il
REPORT AND
RECOMMENDATIONS
Research
Involving
Children
THE NATIONAL
COMMISSION FOR
THE PROTECTION OF
HUMAN SUBJECTS
OF BIOMEDICAL
AND BEHAVIORAL
RESEARCH
m^^ki-^
ia,
REPORT AND
RECOMMENDATIONS
Research
Involving
Children
L\v.A^A ^-v «-«.«, THE NATIONAL
COMMISSION FOR
THE PROTECTION OF
HUMAN SUBJECTS
OF BIOMEDICAL
AND BEHAVIORAL
RESEARCH
DHEW PUBLICATION NO. (OS) 77-0004
|>M
.,1
V
NOTICE
This copy of Research Involving Children is complete, with all text
pages numbered correctly. Due to an error in printing, however, two blank
pages are missing, pages 70 and 122.
J-^.
National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research
Westwood Building, Room 125
5333 Westbard Avenue
^=^^^=^^^^=^^^^==^=======^=== Bethesda, Maryland 20016
September 6, 1977
The President
The White House
Washington, D. C. 20500
Dear Mr. President:
On behalf of the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research, I am pleased to trans-
mit our Report and Recommendations: Research Involving Children .
This is one of several topics of study identified in the mandate to the
Commission under Public Law 93-348, which directs the Commission
to submit its reports and recommendations to the President, the Cong-
ress, and the Secretary of Health, Education, and Welfare.
The involvement of children in research raises particular ethical
concerns because of their reduced autonomy and their incompetency to
give informed consent. Such concerns would not be answered simply
by restricting participation in research to persons who are competent to
consent, for the conduct of research involving children is necessary
not^only to develop^'hew treatment or preventive mejthods for conditions yf^
tliat jeopardize the health of children, but also to protect children from
accepted though unvalidated practices that may be harmful to them. The
Commission has therefore sought to answer the following two questions:
under what conditions is the participation of children in research ethi-,
cally acceptable, and under what conditions may such participation^""^
be authorized by the subjects and their parents. ~
The Commission's answers to these questions are reflected in the
recommendations set forth at the outset of our report. Substantial back-
ground materials, including legal and ethical discussions and statements
of members of the Commission regarding the recommendations, are
also presented in the report. An appendix volume contains a number of
of papers and reports to the Commission that were used in our deliberations.
The Commission continues to find its work most challenging and to be
grateful for the opportunity to provide assistance in areas of wide concern.
Sincerely yours.
.^
Kebineth J» Rya4,/M.
Chairman
National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research
Westwood Building, Room 125
5333 Westbord Avenue
====^=^=========^=====^===^=^==^=^=^= Bethesda, Maryland 20016
September 6. 1977 \
The Honorable Walter F, Mondale
President of the United States Senate
Washington, D.C. 20510
Dear Mr. President:
On behalf of the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research, 1 am pleased to trans-
mit our Report and Recommendations: Research Involving Children .
This is one of several topics of study identified in the mandate to the
Commission under Public Law 93-348, which directs the Commission
to submit its reports and recommendations to the President, the Cong- .
ress, and the Secretary of Health, Education, and Welfare.
The involvement of children in research raises particular ethical
concerns because of their reduced autonomy and their incompetency to
gi^ve informed consent. Such concerns would not be answered simply
B;y^ restricting participation "in ■■researcH to persons who are competent to
consent, for the conduct of research involving children is necessary
not only to develop new treatraent or preventive methods for conditions
that jeopardize the health of children, but also to protect children from
accepted though unvalidated practices that may be harmful to thein. The
Commission has therefore sought to answer the following two questions:
under what conditions is the participation of children in research ethi-
cally acceptable, and under what conditions may such participation
be authorized by the subjects and their parents.
The Commission's answers to these questions are reflected in the
recommendations set forth at the outset of our report. Substantial back-
ground materials, including legal and ethical discussions and statements
of members of the Commission regarding the recommendations, are
also presented in the report. An appendix volume contains a number of
of papers and reports to the Commission that were used in our deliberations.
The Commission continues to find its work most challenging and to be
grateful for the opportunity to provide assistance in areas of wide concern.
Sincerely yours.
Kennetlr^ Ryan, M.D.
Chairman
National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research
Westwood Building, Room 125
5333 Westbard Avenue
— Bethesda, Maryland 20016
September 6, 1977
The Honorable Thomas P. O Neill, Jr.
Speaker of the House of Representatives
Washington. D.C. 20515
Dear Mr. Speaker:
On behalf of the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research, I am pleased to trans-
mit our Report and Recommendations: Research Involving Children.
This is one of several topics of study identified in the mandate to the
Commission under Public Law 93-348, which directs the Commission
to submit its reports and recommendations to the President, the Cong-
ress, and the Secretary of Health, Education, and Welfare.
The involvement of children in research raises particular ethical
concerns because of their reduced autonomy and their incompetency to
give informed consent. Such concerns would not be answered simply
by restricting participation in research to persons who are competent to
consent, for the conduct of research involving children is necessary
not only to develop new treatment or preventive methods for conditions
that jeopardize the health of children, but also to protect children from
accepted though unvalidated practices that may be harmful to them. The
Commission has therefore sought to answer the following two questions:
under what conditions is the participation of children in research ethi-
cally acceptable, and under what conditions may such participation
be authorized by the subjects and their parents.
The Commission's answers to these questions are reflected in the
recommendations set forth at the outset of our report. Substantial back-
i ground materials, including legal and ethical discussions and statements
of members of the Commission regarding the recommendations, are
! also presented in the report. An appendix volume contains a number of
f of papers and reports to the Commission that were used in our deliberations.
Ii
The Commission continues to find its work most challenging and to be
grateful for the opportunity to provide assistance in areas of wide concern.
Sincerely yqurs.
Kehne€fr;i;. Ryan, M. D.
Chairman
National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research
Westwood Building, Room 125
5333 Westbord Avenue
= Be»hesda, Maryland 2(X)16
September 6, 1977
Honorable Joseph A. Califano, Jr. . .
Secretary of Health, Education, and Welfare
Washington, D.C. 20201
Dear Mr. Secretary: ;
On behalf of the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research, 1 am pleased to trans-
mit our Report and Recommendations: Research Involving Children .
This is one of several topics of study identified in the mandate to the
Commission under Public Law 93-348, which directs the Commission
to submit its reports and recommendations to the President, the Cong-
ress, and the Secretary of Health, Education, and Welfare.
The involvement of children in research raises particular ethical
concerns because of their reduced autonomy and their incompetency to
give informed consent. Such concerns would not be answered simply
by restricting participation in research to persons who are competent to
consent, for the conduct of research involving children is necessary
not only to develop new treatment or preventive methods for conditions
that jeopardize the health of children, but also to protect children from
accepted though unvalidated practices that may be harmful to them. The
Commission has therefore sought to answer the following two questions:
under what conditions is the participation of children in research ethi-
cally acceptable, and under what conditions may such participation
be authorized by the subjects and their parents.
The Commission's answers to these questions are reflected in the
recommendations set forth at the outset of our report. Substantial back-
ground materials, including legal and ethical discussions and statements
of members of the Commission regarding the recommendations, are
also presented in the report. An appendix volume contains a number of
of papers and reports to the Commission that were used in our deliberations.
The Commission continues to find its work most challenging and to be
grateful for the opportunity to provide assistance in areas of wide concern.
Sincerely yours.
Kfenneth J. Ryaii/ M. D
Chairman
NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS
OF BIOMEDICAL AND BEHAVIORAL RESEARCH
MEMBERS OF THE COMMISSION
Kenneth John Ryan, M.D., Chairman
Chief of Staff
Boston Hospital for Women
Joseph V. Brady, Ph.D.
Professor of Behavioral Biology
John Hopkins University
Karen Lebacqz, Ph.D.
Associate Professor of Christian Ethics
Pacific School of Religion
Robert E. Cooke, M.D.
President
Medical College of Pennsylvania
David W. Louisell, J.D.
Professor of Law
University of California at Berkeley
Dorothy I. Height
President
National Council of Negro Women, Inc.
Donald W. Seldin, M.D.
Professor and Chairman
Department of Internal Medicine
University of Texas at Dallas
Albert R. Jonsen, Ph.D.
Associate Professor of Bioethics
University of California at San Francisco
Patricia King, J.D.
Associate Professor of Law
Georgetown University Law Center
A
Eliot Stellar, Ph.D.
Provost of the University and
Professor of Physiological Psychology
University of Pennsylvania
Robert H. Turtle, LL.B.
Attorney
VomBaur, Coburn, Simmons & Turtle
Washington, D.C.
NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS
OF BIOMEDICAL AND BEHAVIORAL RESEARCH
COMMISSION STAFF
PROFESSIONAL STAFF
SUPPORT STAFF
Michael S. Yesley, J.D.
Staff Director
Barbara Mishkin, M.A.
Assistant Staff Director
Duane Alexander, M.D.
Pediatrics
Tom L. Beauchamp, Ph.D.
Philosophy
Pamela L. Driscoll
Arlene Line
Marie D. Madigan
Coral M. Nydegger
Erma L. Pender
Lee A. Calhoun, M.A.
Political Science
Bradford H. Gray, Ph.D.
Sociology
SPECIAL CONSULTANTS
Miriam Kelty, Ph.D.
Psychology
Bonnie M. Lee
Administrative Assistant
James J. McCartney, M.A., M.S.
Research Assistant
Robert J. Levine, M.D.
Francis Pizzulli, J.D.
Stephen Toulmin, Ph.D.
Betsy Singer
Public Information Officer
The members of the Commission and its staff
wish to express their deep sorrow at the
untimely death of their friend and respected colleague
David W. Louisell .
His wise counsel and dedication to the work of
the Commission will be greatly missed.
Table of Contents
Introduction xvii
Definitions xix
Recommendations 1
Chapter 1. Why Children are Involved as Research
Subjects 21
2. Nature and Extent of Research Involving
Children 27
3. Survey of Review and Consent Procedures. . . 41
4. Views Presented by the National Minority
Conference on Human Experimentation. ... 49
5. Views Presented at Public Hearings 51
6. Psychological Perspective 71
7. Legal Issues 73
8. Ethical Issues 91
9. Deliberations and Conclusions .123
Introduction
The National Commission for the Protection of Human Subjects of Bio- .
medical and Behavioral Research was established in 1974 under Public Law
93-348 to develop ethical guidelines for the conduct of research involving
human subjects and to make recommendations for the application of such
guidelines to research conducted or supported by the Department of Health,
Education, and Welfare (DHEW). The legislative mandate also directs the
Commission to make recommendations to Congress regarding the protection of
human subjects in research not subject to regulation by DHEW. Classes of
subjects that must receive the Commission's particular attention include
children, prisoners and the institutionalized mentally infirm.
The duties of the Commission with regard to research involving children
are as follows:
The Commission shall identify the requirements for
informed consent to participation in biomedical and
behavioral research by children. .. .The Commission
shall investigate and study biomedical and behavioral
research conducted or supported under programs adminis-
tered by the Secretary [DHEW] and involving children
....to determine the nature of the consent obtained
from such persons or their legal representatives be-
fore such persons were involved in such research; the
adequacy of the information given them respecting the
nature and purpose of the research, procedures to be
used, risks and discomforts, anticipated benefits
from the research, and other matters necessary for
informed consent; and the competence and the free-
dom of the persons to make a choice for or against
involvement in such research. On the basis of such
investigation and study the Commission shall make
such recommendations to the Secretary as it deter-
mines appropriate to assure that biomedical and
xvn
behavioral research conducted or supported under
programs administered by him meets the requirements
respecting informed consent identified by the Com-
mission.
This responsibility is broadened by the provision that the Commission make
recommendations to Congress regarding the protection of subjects (including
children) involved in research not subject to regulation by DHEW.
To discharge its duties under this mandate, the Commission studied
the nature and extent of research involving children, the purposes for
which such research is conducted, and the issues surrounding the parti-
cipation of children in research. Representatives from professional socie-
ties, federal agencies and public interest groups, as well as parents and
other members of the public, presented their views to the Commission at a
public hearing. The National Minority Conference on Human Experimentation,
convoked by the Commission to assure that viewpoints of minorities would be
expressed, made recommendations to the Commission on research involving
children. The Commission also reviewed papers and reports prepared under
contract, including papers on informed consent and a survey of actual
practices in research involving children. Finally, the Commission con-
ducted extensive deliberations in public and developed recommendations
on the participation of children in research.
The Commission's recommendations are set forth at the outset of this
report, followed by chapters presenting background information, sunmaries
of reports and views presented to the Commission, an analysis of the law
xvm
with respect to research involving children, critiques of various ethical
arguments, and statements of members of the Commission regarding the recom-
mendations. An appendix to this report contains the text of reports and
papers prepared under contract, other materials reviewed by the Commission
in the course of its study and deliberations, and a selective bibliography.
Definitions . For the purpose of this report:
1. Children are persons who have not attained the .lega^^
sent to general medical care as determined under the applicable law of
the jurisdiction in which the research will be conducted.
Comment: P.L. 93-348 defines children as "individuals who have not
attained the legal age of consent to participate in research as determined
under the applicable law of the jurisdiction in which the research is to
be conducted." The Corranission notes that the legal age of consent to parti-
cipate in research is not specifically defined in local jurisdictions. For
the purposes of this report, therefore, the Commission has used the age of
consent to general medical care (as distinguished from age of consent for
treatment of specific conditions, such as pregnancy, drug addiction or .
venereal disease). ^ * J ^ > ^ '^ ^
2. Research is a formal investigation designed to develop or contri-
bute to general izable knowledge.
XIX
Comment: A research project generally is described in a protocol that
sets forth explicit objectives and formal procedures designed to reach those
objectives. The protocol may include therapeutic and other activities in-
tended to benefit the subjects, as well as procedures to evaluate such acti-
vities. Research objectives range from understanding normal and abnormal
physiological or psychological functions or social phenomena, to evaluating
diagnostic, therapeutic or preventive interventions and variations in ser-
vices or practices. The activities or procedures involved in research may
be invasive or noninvasive and include surgical interventions; removal of
body tissues or fluids; administration of chemical substances or forms of
energy; modification of diet, daily routine or service delivery; alteration
of environment; observation; administration of questionnaires or tests;
randomization; review of records, etc.
3. ' Minimal risk is the probability and magnitude of physical or psycho-
logical harm that is normally encountered in the daily lives, or in the
routine medical or psychological examination, of healthy children.
Comment: In any assessment of the degree of risk to children that is
presented by proposed research activities, the age of the prospective research
subjects should be taken into account. The possible effects of disruption of
normal routine, separation from parents, or unusual discomfort should be con-
sidered, as well as more obvious physical or psychological harms. Examples
of medical procedures presenting no more than minimal risk would include
routine immunization, modest changes in diet or schedule, physical examina-
XX
/ &r' lA-fUV C, ^ Di%.^..t3m-yv Fj C.^-!t.i!Vt^l^ \ / &> pfVV \'.-^:>
tion, obtaining blood and urine specimens, and developmental assessments.
Similarly, many routine tools of behavioral research, such as most ques-
tionnaires, observational techniques, noninvasive physiological monitoring,
psychological tests and puzzles, may be considered to present no more than
minimal risk. Questions about some topics, however, may generate such
anxiety or stress as to involve more than minimal risk. Research in which
information is gathered that could be harmful if disclosed should not be
considered of minimal risk unless adequate provisions are made to preserve
confidentiality. Research in which information will be shared with persons
or institutions that may use such information against the subjects should
be considered to present more than minimal risk.
4. Institutional Review Board (IRB) is (1) a committee required under
P.L. 93-348 and approved by the Department of Health, Education, and Welfare
to review research involving human subjects at an institution receiving sup-
port for such research under the Public Health Service Act, or (2) any sub-
stantially similar committee which reviews research involving human subjects
that is conducted, supported or regulated by a federal agency or department.
XXI
Recommendations
The National Commission for the Protection of Human Subjects of Bio-
medical and Behavioral Research makes the following recommendations for
research involving children to:
The Secretary of Health, Education, and Welfare, with respect to
research that is subject to his regulation, l.o,., research conducted or
supported under programs administered by him and research reported to him
in fulfillment of regulatory requirements; and
The Congress, with respect to research that is not subject to regu-
lation by the Secretary of Health, Education, and Welfare.
Recommendation (1) Since the Commission finds that re-
search INVOLVING children IS IMPORTANT FOR THE HEALTH AND WELL-
BEING OF ALL CHILDREN AND CAN BE CONDUCTED IN AN EThLICAL MANNER,
THE Commission recommends that such research be conducted and
SUPPORTED, subject TO THE CONDITIONS SET FORTH IN THE FOLLOWING
RECOMMENDATIONS.
Comment : The Commission recognizes the importance of safeguarding and
improving the health and well-being of children, because they deserve the
best care that society can reasonably provide. It is necessary to learn
more about normal development as well as disease states in order to develop
methods of diagnosis, treatment and prevention of conditions that jeopardize
the health of children, interfere with optimal development, or adversely
affect well-being in later years. Accepted practices must be studied as
well, for although infants cannot survive without continual support, the
effects of many routine practices are unknown and some have been shown to
be harmful . ■' ■
Much research on childhood disorders or conditions necessarily involves
children as subjects. The benefits of this research may accrue to the sub-
jects directly or to children as a class. The Commission considers, there-
fore, that the participation of children in research related to their condi-
tions should receive the encouragement and support of the federal government.
The Commission recognizes, however, that the vulnerability of children,
which arises out of their dependence and immaturity, raises questions about
the ethical acceptability of involving them in research. Such ethical pro-
blems can be offset, the Commission believes, by establishing conditions
that research must satisfy to be appropriate for the involvement of children.
Such conditions are set forth in the following recommendations.
^ .5<i^r^^^ ••■■■■ ■ .-
A.c^^r- Recommendation (2) Research involving children may be con-
A DUCTED OR supported PROVIDED AN INSTITUTIONAL REVIEW BOARD HAS
DETERMINED THAT: (A) THE RESEARCH IS SCIENTIFICALLY SOUND AND
SIGNIFICANT; (B) WHERE APPROPRIATE^ STUDIES HAVE BEEN CONDUCTED
FIRST ON ANIMALS AND ADULT HUMANS, THEN ON OLDER CHILDREN, PRIOR
TO INVOLVING INFANTS; (C) RISKS ARE MINIMIZED BY USING THE SAFEST
PROCEDURES CONSISTENT WITH SOUND RESEARCH DESIGN AND BY USING PRO"
/ CEDURES PERFORMED FOR DIAGNOSTIC OR TREATMENT PURPOSES WHENEVER
,J^
FEASIBLE; (D) ADEQUATE PROVISIONS ARE MADE TO PROTECT THE PRI-
VACY OF CHILDREN AND THEIR PARENTS^ AND TO MAINTAIN CONFIDEN-
TIALITY OF DATA; (E) SUBJECTS WILL BE SELECTED IN AN EQUITABLE
MANNER; AND (F) THE CONDITIONS OF ALL APPLICABLE SUBSEQUENT 'Z ■?4.f\^
RECOMMENDATIONS ARE MET. - ■ T^'r^^
Comment : This recommendation sets forth general conditions that
should apply to all research involving children. Such research must also
satisfy the conditions of one or more of Pvecommendations (3) through (5),
as applicable; Recommendation (7); Recommendation (8), if permission of
parents or guardians is not a reasonable requirement; Recommendation (9),
if the subjects are wards of the state; and Recommendation (10), if the
subjects are institutionalized.
Respect for human subjects requires the use of sound methodology appro-
priate to the discipline. The time and inconvenience requested of subjects • >
should be justified by the soundness of the research and its design, even if
no more than minimal risk is involved. In addition, research involving ^
children should satisfy a st anda rd of scientific s i_ftn i f ixa nee , [_s i n c e these '
subjects are less capable than adults of determining for themselves whether
to participate. If necessary, the IRB should obtain the advice of consultants
to assist in determining scientific soundness and significance. (The Commis-
sion will consider problems related to the determination of scientific sound-
ness and significance in a future report on the performance of IRBs.)
Whenever possible, research involving risk should be conducted first
on animals and adult humans in order to ascertain the degree of £isk and
the likelihood of generating useful knowledge. Sometimes this is not rele-
vant or possible, as when the research is designed to study disorders or
functions that have no parallel in animals or adults. In such cases, studies
involving risk should be initiated on older children to the extent feasible
prior to including infants, because older children are less vulnerable and
they are better able to understand and to assent to participation. In addi-
tion, they are more able to communicate about any physical or psychological
effects of such participation.
In order to minimize risk, investigators should use the safest proce-
dures consistent with good research design and should make use of information
or materials obtained for diagnostic or treatment purposes whenever feasi-
ble. For example, if a blood sample is needed, it should be obtained from
samples drawn for diagnostic purposes whenever it is consistent with research
requirements to do so. . : : .
Adequate measures should be taken to protect the privacy of children
and their families, and to maintain the confidentiality of data. The ade-
quacy of procedures for protecting confidentiality should be considered in
light of the sensitivity of the data to be collected (^.e. , the extent to
which disclosure could reasonably be expected to be harmful or embarrassing).
Subjects should be selected in an equitable manner, avoiding overutili-
zation of any one group of children based solely upon administrative con-
venience or availability of a population living in conditions of social or
economic deprivation. The burdens of participation in research should be
equitably distributed among the segments of our society, no matter how large
or small those burdens may be.
In addition to the foregoing requirements, research must satisfy the
conditions of the following recommendations, as applicable.
Recommendation (5) Research that does not involve greater
than minimal risk to children may be conducted or supported pro-
VIDED AN Institutional Review Board has determined that: (A)
THE conditions OF RECOMMENDATION (2) ARE METj AND (B) ADEQUATE
PROVISIONS ARE MADE FOR ASSENT OF THE CHILDREN AND PERMISSION OF
THEIR PARENTS OR GUARDIANS^ AS SET FORTH IN RECOMMENDATIONS (7)
AND (8).
Comment : If the IRB determines that proposed research will present no
more than minimal risk to children, the research may be conducted or sup-
ported provided the conditions of Recorrenendation (2) are met and appropriate
provisions are made for parental permission and the children's assent, as
described in Recommendations (7) and (8) below. If the IRB is unable to
determine that the proposed research will present no more than minimal risk
to children, the research should be reviewed under Recommendations (4), (5)
and (6), as applicable.
Recommendation (4) Research in which more than minimal risk
TO children is presented by an intervention that H0LDSJ)UT jhe
prospect of direct benefit for the individual subjects^ or by a
monitoring procedure required for the well-being of the subjects,
may be conducted or supported provided an institutional review
Board has determined that:
(A) such risk is justified BY THE ANTICIPATED BENEFIT
TO THE subjects;
(B) THE RELATION OF ANTICIPATED BENEFIT TO SUCH RISK
IS AT LEAST AS FAVORABLE TO THE SUBJECTS AS THAT PRE-
SENTED BY AVAILABLE ALTERNATIVE APPROACHES.
(C) THE CONDITIONS OF RECOMMENDATION (2) ARE METj AND
(D) ADEQUATE PROVISIONS ARE MADE FOR ASSENT OF THE
CHILDREN AND PERMISSION OF THEIR PARENTS OR GUARDIANS,
AS SET FORTH IN RECOMMENDATIONS (7) AND (8).
Comment : The Commission emphasizes that the purely investigative pro-
cedures in research encompassed by Recommendation (4) should entail no more
than minimal risk to children. Greater risk is permissible under this recom-
mendation only if it is presented by an intervention that holds out the pros-
pect of direct benefit to the individual subjects or by a procedure necessary
to monitor the effects of such intervention in order to maintain the well-
being of these subjects (e.g., obtaining samples of blood or spinal fluid in
order to determine drug levels that are safe and effective for the subjects).
Such risk is acceptable, for example, when all available treatments for a
serious illness or disability have been tried without success, and the re-
maining option is a new intervention under investigation. The expectation
of success should be scientifically sound to justify undertaking whatever
risk is involved. It is also appropriate to involve children in research ■
when accepted therapeutic, diagnostic or preventive methods involve risk
or are not entirely successful, and new biomedical or behavioral procedures
under investigation present at least an equally favorable risk-benefit
ratio. The IRB should evaluate research protocols of this sort in the same
way that comparable decisions are made in clinical practice. It should com-
pare the risk and anticipated benefit of the intervention under investiga-
tion (including the monitoring procedures necessary for care of the child)
with those of available alternative methods for achieving the same goal,
and should also consider the risk and possible benefit of attempting no
intervention whatsoever.
To determine the overall acceptability of the research, the risk and
anticipated benefit of activities described in a protocol must be evaluated
individually as well as collectively, as is done in clinical practice. Re-
search protocols meeting the criteria regarding risk and benefit may be
conducted or supported provided the conditions of Recommendation (2) are
fulfilled and the requirements for assent of the children and for permis- •
sion and participation of their parents or guardians, as set forth in Recom-
mendations (7) and (8), will be met. If the research also includes a purely
investigative procedure presenting more than minimal risk, the research
should be reviewed under Recommendation (5) with respect to such procedure.
R ecommendation (5) Research in which more than minimal risk
TO children is presented by an intervention that does not hold
OUT THE prospect OF DIRECT BENEFIT FOR THE INDIVIDUAL SUBJECTS^
or by a monitoring procedure not required for the well-being
of the subjects, may be conducted or supported provided an
Institutional Review Board has determined that:
(A) SUCH RISK represents A MINOR INCREASE OVER MINI"
: MAL RISKj
(B) SUCH INTERVENTION OR PROCEDURE PRESENTS EXPERIENCES
TO SUBJECTS THAT ARE REASONABLY COMMENSURATE WITH THOSE
INHERENT IN THEIR ACTUAL OR EXPECTED MEDICAL, PSYCHO-
LOGICAL OR SOCIAL SITUATIONS, AND IS LIKELY TO YIELD
GENERALIZABLE KNOWLEDGE ABOUT THE SUBJECTS' DISORDER
OR CONDITION;
(C) THE ANTICIPATED KNOWLEDGE IS OF VITAL IMPORTANCE
FOR UNDERSTANDING OR AMELIORATION OF THE SUBJECTS' DIS-
ORDER OR CONDITION;
(D) THE CONDITIONS OF RECOMMENDATION (2) ARE MET; AND
(E) ADEQUATE PROVISIONS ARE MADE FOR ASSENT OF THE
CHILDREN AND PERMISSION OF THEIR PARENTS OR GUARDIANS,
AS SET FORTH IN RECOMMENDATIONS (7) AND (8).
Comment : An IRB must determine that three special criteria are met in
order to approve research presenting more than minimal risk but no direct
benefit to the individual subjects. First, the increment in risk must be
no more than a minor increase over minimal risk. The IRB should consider
the degree of risk presented by the research from at least the following
four perspectives: a common-sense estimation of the risk; an estimation
based upon investigators' experience with similar interventions or proce-
dures; any statistical information that is available regarding such inter-
ventions or procedures; and the situation of the proposed subjects. Second,
the research activity must be commensurate with (-c.e., reasonably similar
to) procedures that the prospective subjects and others with the specific
disorder or condition ordinarily experience (by virtue of having or being
treated for that disorder or condition). Finally, the research must hold
out the promise of significant benefit in the future to children suffering
from or at risk for the disorder or condition (including, possibly, the
subjects themselves). If necessary, the advice of scientific consultants
should be obtained to assist in determining whether the research is likely
to provide knowledge of vital importance to understanding the etiology or
pathogenesis, or developing methods for the prevention, diagnosis or treat-
ment, of the disorder or condition affecting the subjects.
The requirement of commensurability of experience should assist children
who can assent to make a knowledgeable decision about their participation in
research, based on some familiarity with the intervention or procedure and
its effects. More generally, commensurability is intended to assure that
participation in research will be closer to the ordinary experience of the
subjects. The use of procedures that are familiar or similar to those used
in treatment of the subjects should not, however, be used as a major justi-
fication for their participation in research, but rather as one of several
criteria regarding the acceptability of such participation.
In addition to these special criteria, the IRB should assure that the
conditions of Recommendation (2) are fulfilled and the requirements for
assent of the children and permission and participation of their parents
or guardians, as set forth in Recommendations (7) and (8), will be met. If
the proposed research includes an intervention or procedure from which the
subjects may derive direct benefit, it should also be reviewed under Recom-
mendation (4) with respect to that intervention or procedure.
Recommendation (6) Research that cannot be approved by an
Institutional Review Board under Recommendations (3), (4) and
(5), as applicable^ may be conducted or supported provided an
Institutional Review Board has determined that the research
presents an opportunity to understand, prevent or alleviate a
serious problem affecting the health or welfare of children
and, in addition, a national ethical advisory board and, fol-
lowing opportunity for public review and comment, the secretary
of the responsible federal department (or highest official of
the responsible federal agency) have determined either (A) THAT
the research satisfies THE CONDITIONS OF RECOMMENDATIONS (3),
(4) AND (5), AS APPLICABLE, OR (B) THE FOLLOWING:
(I) THE RESEARCH PRESENTS AN OPPORTUNITY TO UNDER-
STAND, PREVENT OR ALLEVIATE A SERIOUS PROBLEM AF-
. . FECTING THE HEALTH OR WELFARE OF CHILDREN.;
(II) THE CONDUCT OF THE RESEARCH WOULD NOT VIOLATE
THE PRINCIPLES OF RESPECT FOR PERSONS, BENEFICENCE
AND JUSTICE;
10
(hi) the conditions of Recommendation (2) are met;
AND
(IV) ADEQUATE PROVISIONS ARE MADE FOR ASSENT OF THE .
CHILDREN AND PERMISSION OF THEIR PARENTS OR GUARDIANS,
AS SET FORTH IN RECOMMENDATIONS (7) AND (8).
Comment : If an IRB is unable for any reason to determine that proposed
research satisfies the conditions of Recommendations (3), (4) and (5), as
applicable, the IRB may nevertheless certify the research for review and
possible approval by a national ethical advisory board and the Secretary
of the responsible department. Such review is contingent upon an IRB's
determination that the research presents an opportunity to understand,
prevent or alleviate a serious problem affecting the health or welfare of
children. Thereafter, the research should be reviewed by the national board
and Secretary, with opportunity for public comment, to determine whether
the conditions of Recommendations (3), (4) and (5), as applicable, are
satisfied, or, alternatively, the research is justified by the importance
of the knowledge sought and would not contravene principles of respect for
persons, beneficence and justice that underlie these recommendations. In
the latter instance, commencement of the research should be delayed pending
Congressional notification and a reasonable opportunity for Congress to take
action regarding the proposed research.
The provision for national review and approval under Recommendations
(3), (4) and (5) is intended to fit the situation where an IRB has diffi-
culty in applying those recommendations but considers the research of suf-
11
ficient importance to warrant national review. Such difficulty may be
resolved by a determination on the national level pursuant to Recommenda-
tion (6)(A) that the research does satisfy the conditions of the applica-
ble earlier recommendations. Alternatively, the national review may deter-
mine either that the research satisfies the conditions of Recommendation
C6)(B) or that it should not be conducted.
The Commission believes that only research of major significance, in
the presence of a serious health problem, would justify the approval of
research under Recommendation (6)(B). The problem addressed must be a
grave one, the expected benefit should be significant, the hypothesis re-
garding the expected benefit must be scientifically sound, and an equita-
ble method should be used for selecting subjects who will be invited to
participate. Finally, appropriate provisions should be made for assent of
the subjects and permission and participation of parents or guardians.
Recommendation (7) In addition to the determinations required
under the foregoing recommendations^ as applicable^ the institu-
TIONAL Review Board should determine that adequate provisions
ARE made for: (A) soliciting THE ASSENT OF THE CHILDREN (WHEN
capable) AND THE PERMISSION OF THEIR PARENTS OR GUARDIANS; ANDy
WHEN APPROPRIATE, (B) MONITORING THE SOLICITATION OF ASSENT AND
PERMISSION, AND INVOLVING AT LEAST ONE PARENT OR GUARDIAN IN THE
CONDUCT OF THE RESEARCH. A CHILD's OBJECTION TO PARTICIPATION
IN RESEARCH SHOULD BE BINDING UNLESS THE INTERVENTION HOLDS OUT
12
A PROSPECT OF DIRECT BENEFIT THAT IS IMPORTANT TO THE HEALTH
OR WELL-BEING OF THE CHILD AND IS AVAILABLE ONLY IN THE CON-
TEXT OF THE RESEARCH.
Comment : The Conmission uses the term parental or guardian "permis-
sion," rather than "consent," in order to distinguish what a person may do
autonomously (consent) from what one may do on behalf of another (grant
permission). Parental permission normally will be required for the parti-
cipation of children in research. In addition, assent of the children
should be required when they are seven years of age or older. The Commis-
sion uses the term "assent" rather than "consent" in this context, to dis-
tinguish a child's agreement from a legally valid consent.
Parental or guardian permission, as used in this recommendation, refers
to the permission of parents, legally appointed guardians, and others who
care for a child in a reasonably normal family setting. The last category
might include, for example, step-parents or relatives such as aunts, uncles
or grandparents who have established a continuing, close relationship
with the child. Recommendation (8) describes circumstances in which the
IRB may determine that the permission of parents or guardians is not appro-
priate because of the nature of the subject under investigation (e.g.,
contraception, drug abuse) or because of a failure in the relationship with
the child (e.g., child abuse, neglect).
Parental or guardian permission should reflect the collective judgment
of the family that an infant or child may participate in research. There
13
ars some research projects for which documented permission of one parent
or guardian should be sufficient, such as research involving no more than
minimal risk (as described in Recommendation (3)), or research in which
risks or discomforts are related to a therapeutic, diagnostic or preventive
Intervention (as described in Recommendation (4)). In such cases, it may
be assumed that the person giving formal permission is reflecting a family
consensus. For research that is described in Recommendations (5) and (6),
the permission of both parents should be documented unless one parent is
deceased, unknown, incompetent or not reasonably available, or the child
has a guardian or belongs to a single-parent family [l.n., when only one
person has legal responsibility for the care, custody and financial sup-
port of the child). The IRB should determine for each project whether per-
mission of one or both parents should be required, a substitute mechanism
may be used, or the provision may be waived. In making such determination,
the IRB should consider the nature of the activities described in the re-
search protocol and the age, status and condition of the subjects.
The IRB should assure that children who will be asked to participate
in research described in Recommendation (5) are those with good relation-
ships with their parents or guardians and their physician, and who are re-
ceiving care in supportive surroundings. Projects approved under Recom-
mendations (4) and (5) may also require scrutiny of this sort. The IRB
may wish to appoint someone to assist in the selection of subjects and to
review the quality of interaction between parents or guardian and child.
A member of the board or a consultant such as the child's pediatrician, a
psychologist, a social worker, a pediatric nurse, or other experienced and
perceptive person would be appropriate. The IRB should be particularly
sensitive to the difficulties surrounding permission when the investigator
is the treating physician to whom the parents or guardian may feel an
obligation. . ;. -; . ■
Because of the dependence of infants, the traditional role of parents
as protectors, and the general authority of parents to determine the care
and upbringing of their children, the IRB may determine that small children
should participate in certain research only if the parents or guardians
participate themselves by being present during some or all of the conduct
of the research. This role will vary according to the nature of the re-
search, the risk involved, the extent to which the research entails possi-
bly disturbing deviations from normal routine, and the age and condition .
of the children. As a general rule, when infants participate in research
that may cause physical discomfort or emotional stress and involves a sig-
nificant departure from normal routine, a parent or guardian should be pre-
sent. However, if discomfort arises only as a result of therapeutic inter-
ventions that must continue over a considerable period of time, the con-
tinual presence of parents need not be required. Parental presence during
the conduct of much behavioral research may not be feasible or warranted,
especially with older children. Generally, parents or guardians should be
sufficiently involved in the research to understand its effects on their
children and be able to intervene, if necessary.
15
The Commission believes that children who are seven years of age or
older are generally capable of understanding the procedures and general
purpose of research and of indicating their wishes regarding participation.
Their assent should be required in addition to parental permission. How-
ever, if any child over six years of age is incapacitated so that he or
she cannot reasonably be consulted, then parental permission should be
sufficient, as it is for infants. The objection of a child of any age
to participation in research should be binding except as noted below.
If the research protocol includes an intervention from which the sub-
jects might derive significant benefit to their health or welfare, and that
intervention is available only in a research context, the objection of a
small child may be overridden. Such would be the case, for example, with
a new drug that is not approved by the Food and Drug Administration for
general distribution until safety and efficacy have been demonstrated in
controlled clinical trials. Access to a drug under investigation generally
requires participation in the research. Similar restrictions may be placed
on other innovative therapies as a precaution. As children mature, their
ability to perceive and act in their own best interest increases; thus, their
wishes with respect to such research should carry increasingly more weight.
When school-age children disagree with their parents regarding participation
in such research, the IRB may wish to have a third party discuss the matter
with all concerned and be present during the consent process. Although
parents may legally override the objections of school-age children in such
cases, the burden of that decision becomes heavier in relation to the maturity
of the particular child.
16
Disclosure requirements for assent and permission are the same as
those for informed consent. Similarly, children and parents or guardians
should be free from duress. In order to assure understanding and freedom
of choice, the IRB may determine that there is a need for an advocate to
be present during the decision-making process. The need for third-party
involvement in this process will vary according to the risk presented by
the research and the autonomy of the subjects. The advocate should be an
individual who has the experience and perceptiveness to fulfill such a ..
role and who is not related in any way (except in the role as advocate or
member of the IRB) to the research or the investigators.
Finally, the IRB should pay particular attention to the explanation
and consent form, if any, to assure that appropriate language is used. .
Recommendation (8) If the Institutional Review Board deter-
mines THAT a research PROTOCOL IS DESIGNED FOR CONDITIONS OR A
SUBJECT POPULATION FOR WHICH PARENTAL OR GUARDIAN PERMISSION IS
NOT A REASONABLE REQUIREMENT TO PROTECT THE SUBJECTS^ IT MAY
WAIVE SUCH REQUIREMENT PROVIDED AN APPROPRIATE MECHANISM FOR
PROTECTING THE CHILDREN WHO WILL PARTICIPATE AS SUBJECTS IN THE
RESEARCH IS SUBSTITUTED, ThE CHOICE OF AN APPROPRIATE MECHANISM
SHOULD DEPEND UPON THE NATURE AND PURPOSE OF THE ACTIVITIES DES-
CRIBED IN THE PROTOCOL^ THE RISK AND ANTICIPATED BENEFIT TO THE
RESEARCH SUBJECTS^ AND THEIR AGE, STATUS AND CONDITION.
Comment: Circumstances that would justify modification or waiver of the
requirement for parental or guardian permission includes: (1) research designed
17
to identify factors related to the incidence or treatment of certain condi-
tions in adolescents for which, in certain jurisdictions, they legally may
receive treatment without parental consent; (2) research in which the sub-
jects are "mature minors" and the procedures involved entail essentially no
more than minimal risk that such individuals might reasonably assume on
their own; (3) research designed to understand and meet the needs of neg-
lected or abused children, or children designated by their parents as "in
need of supervision"; and (4) research involving children whose parents are
legally or functionally incompetent.
There is no single mechanism that can be substituted for parental per-
mission in every instance. In some cases the consent of mature minors should
be sufficient. In other cases court approval may be required. The mechanism
invoked will vary with the research and the age, status and condition of the
prospective subjects.
A number of states have specific legislation permitting minors to con-
sent to treatment for certain conditions (e.g., pregnancy, drug addiction,
venereal diseases) without the permission (or knowledge) of their parents.
If parental permission were required for research about such conditions, it
would be difficult to develop improved methods of prevention and therapy
that meet the special needs of adolescents. Therefore, assent of such
mature minors should be considered sufficient with respect to research about
conditions for which they have legal authority to consent on their own to
treatment. An appropriate mechanism for protecting such subjects might be
to require that a clinic nurse or physician, unrelated to the research.
18
explain the nature and the purpose of the research to prospective subjects,
emphasizing that participation is unrelated to provision of care.
Another alternative might be to appoint a social worker, pediatric
nurse, or physician to act as surrogate parent when the research is designed,
for example, to study neglected or battered children. Such surrogate parents
would be expected to participate not only in the process of soliciting the
children's cooperation but also in the conduct of the research, in order to
provide reassurance for the subjects and to intervene or support their de-
sires to withdraw if participation becomes too stressful.
Recommendation (9) Children who are wards of the state should
NOT BE included IN RESEARCH APPROVED UNDER RECOMMENDATIONS (5) OR
(6) UNLESS SUCH RESEARCH IS: (A) RELATED TO THEIR STATUS AS OR-
PHANS, ABANDONED CHILDREN, AND THE LIKE; OR (B) CONDUCTED IN A
SCHOOL OR SIMILAR GROUP SETTING IN WHICH THE MAJORITY OF CHILDREN
INVOLVED AS SUBJECTS ARE NOT WARDS OF THE STATE. If SUCH RESEARCH
IS APPROVED, THE INSTITUTIONAL REVIEW BOARD SHOULD REQUIRE THAT
AN ADVOCATE FOR EACH CHILD BE APPOINTED, WITH AN OPPORTUNITY TO
INTERCEDE THAT WOULD NORMALLY BE PROVIDED BY PARENTS.
Comment : It is important to learn more about the effects of various
settings in which children who are wards of the state may be placed, as well
as about the circumstances surrounding child abuse and neglect, in order to
improve the care that is provided for such children by the community. Also,
it is important to avoid embarrassment or psychological harm that might re-
19
suit from excluding wards of the state from research projects in which
their peers in a school, camp or other group setting will be participating.
Provision must be made to permit the conduct of such studies in ways that
will protect the children involved, even though no parents or guardians
are available to act in their behalf.
To this end, the IRB reviewing such research should evaluate the rea-
sons for including wards of the state as research subjects and assure that
such children are not the sole participants in a research project unless the
research is related to their status as orphans, abandoned children, and
the like. The IRB should require, as a minimum, that an advocate for each
child be appointed to intercede, when appropriate, on the child's behalf.
The IRB may also require additional protections, such as prior court approval.
Recommendation (10) Children who reside in institutions for
THE mentally infirm OR WHO ARE CONFINED IN CORRECTIONAL FACILI-
TIES SHOULD PARTICIPATE IN RESEARCH ONLY IF THE CONDITIONS RE-
GARDING RESEARCH ON THE INSTITUTIONALIZED MENTALLY INFIRM OR
ON PRISONERS (AS APPLICABLE) ARE FULFILLED IN ADDITION TO THE
CONDITIONS SET FORTH HEREIN.
NOTE: The foregoing recommendations were adopted unanimously with the ex-
ception of Recommendation (5), from which Cormiissi oners Cooke and Turtle
dissented.
20
Chapter 1. Why Children are Involved as Research Subjects
The argument in favor of conducting research involving children rests '
on a combination of two factors: the absence, in numerous instances, of
a suitable alternative population of research subjects, and the consequences
of not conducting research involving children in those instances. Such con-
sequences might include the perpetuation of harmful practices, the intro-
duction of untested practices, and the failure to develop new treatments
for diseases that affect children.
The lack of an alternative population . Possible alternative popula-
tions for research involving children are animals and adult humans, but
there are limitations to both. No animal model has been found for a num-
ber of diseases that affect children or adults, such as cystic fibrosis
and Down's syndrome. Furthermore, animal models are inappropriate for
studying certain processes that are uniquely human, such as development
of speech and cognitive functions. The amount of brain development that
occurs in humans after birth has no parallel in the animal world, and stud-
ies of such development must be done in humans. Even normal biological
measures or functions in animals, such as blood sugar levels or drug meta-
bolism, are not consistent from one animal species to another and cannot
be extrapolated to humans; thus, it eventually becomes necessary to examine
the function in human subjects.
There are also no adult models for disorders that are unique to child-
hood, such as hyaline membrane disease, erythroblastosis fetalis, and in-
21
fantile autism. Studies of normal development and of such phenomena as
the "critical period" and child-parent interaction, by their very nature,
can be conducted only in children. Research involving children is impor-
tant, also, because both in sickness and in health, the child is not a
small adult, and, consequently, results of studies on adults cannot be
directly extrapolated to children. For example, administration of intra-
venous fluids to infants or children based on adult requirements would
be disastrous, providing either too much or too little of various sub-
stances. It was only by studying normal constituents of body fluids and
their metabolism in normal infants and children that requirements for
specific age groups could be identified and intravenous fluid therapy could
be utilized. A more obvious difference between children and adults is
in their food requirements, not only in type and nutrients but in calories
-- an infant provided calories based on adult requirements would soon
starve. An assumption that drugs which are useful and safe in adults
are effective and safe in children, and that it is necessary only to ad-
just dosage on the basis of body weight or surface area, is likewise not
only fallacious but also dangerous, as exemplified by the examples of
chloramphenicol and sulfisoxazole cited below.
■ Just as children are not small adults, it is also erroneous to con-
sider all children as a homogeneous category. A child is a developing and
constantly changing organism: the newborn infant, in its body composition
and metabolism as well as its response to drugs and stimuli, differs from
the toddler; the early school-age child differs from the pubertal adolescent.
22
Growth imposes its own special set of constraints and challenges. Conse-
quently there is a need not only for research on children, but across the
full spectrum of childhood.
The consequences of not involving children in research . Prohibiting
children's participation in research would impede innovative efforts to
develop new treatments for diseases that affect children, while research
to prevent or treat adult diseases would continue. Even research efforts
on adult diseases would be hampered, as many of the most common and serious
diseases that affect adults, such as atherosclerosis, probably have their
origins in childhood. Many adults with cystic fibrosis or juvenile diabetes
mellitus would not be alive today without the benefit of research that in-
volved children.
Prohibiting children's participation in research would also result
in the introduction of innovative practices without benefit of research
or evaluation. The history of misadventures from such untested and un-
validated Innovation argues as strongly for research as does the failure
to innovate that would result from impeding research. For example, intro-
duction of the practice of supplying oxygen in high concentrations to pre-
mature infants with hyaline membrane disease to enable them to survive was
successful in many cases. However, the price paid for this course of ac-
tion was the blinding of thousands of children due to retrolental fibro-
plasia before it was found that high oxygen levels had a toxic effect on
the blood vessels supplying the retina in premature infants.
23
Another iatrogenic disease whose cause went undetected for years was
the "gray-baby syndrome," which resulted in the death of many newborn in-
fants until a research project (terminated early because the results were
so clear) demonstrated that the drug chloramphenicol was responsible. This
drug was an effective and generally safe antibiotic in adults, and it had
been extended to use in children and infants without special study. The
use of chloramphenicol for newborn infants was quickly abandoned when re-
search demonstrated that poisoning occurred from the toxic levels of the
drug that accumulated, because the enzyme system that metabolizes the drug
is inadequately developed in the newborn. Another antibacterial agent,
sulfisoxazole, was also abandoned for use in newborn infants after it was
shown to cause severe neural injury (kernicterus) and cerebral palsy by
binding to serum albumin so that bilirubin could not be bound and was
free to damage nerve cells. Use of Vitamin K to prevent hemorrhagic
disease of the newborn was a major advance, but its use in excessive doses
also produced many cases of kernicterus due to its destruction of red blood
cells with resultant increase in bilirubin levels, until research demon-
strated this danger and established a safe and effective dose.
Even such a seemingly simple matter as feeding and hydrating a new-
born infant has, without proper research, been subject to faddism and un-
tested innovation. Because premature infants tend to look edematous, for
years it was routine practice to give them no food or water for 48 to 72
hours after birth, with a high incidence of brain damage ensuing from an
excessive amount of sodium in the blood of the few who survived the drying
out procedure. Despite abandonment of such practices and conduct of much
24
research, there still exists no general agreement on when to begin feedings
for premature infants and how much of what to give.
Another standard treatment, whose adverse effects continue to be mani-
fested 20 to 30 years later in the form of radiation-induced thyroid can-
cer, was prophylactic radiation to the neck and chest, used in the 1940's
to shrink an infant's thymus. This treatment was administered on the hypo-
thesis that it would prevent the sudden infant death syndrome, with no basis
in fact other than the observation that many victims of the syndrome had an
enlarged thymus at autopsy. .'
Nonmedical practices also may have harmful effects, and be equally
ill-founded but firmly entrenched, and modifiable only by research. For
example, only when research was conducted were the ill effects of the
routine practices of institutionalization on child development demonstrated,
and changes in practices initiated.
There are other standard practices whose effects remain matters of
speculation. For example, concern is currently being expressed over the
practice of isolating premature infants from their parents in intensive
care nurseries, based on evidence from research that shows the importance
of very early physical contact between the mother and infant for the esta-
blishment of parental bonding, and the significantly higher incidence of
child abuse of premature infants. . ■.
In sum, there is historical evidence of undesirable consequences re-
sulting from the introduction of innovations in pediatric practice without
25
adequate research, and there are many areas of inquiry that are important
for improving the health and well-being of children (and adults), and for
which there is no research population other than children.
26
Chapter 2, The Nature and Extent of Research Involving Children
Children participate as subjects in a wide variety of research under-
takings. A survey of government agencies' research activities involving
children during fiscal year 1975 provides an indication of the diversity of
these projects, and may be considered a reflection of nongovernment-supported
research with children as well. This survey is based on reports provided to
the Commission by components of DHEW and on information compiled by the Social
Research Group of George Washington University. It should be noted that the
definitions of "child" vary among agencies (sometimes including individuals
through age 25); similarly, some agencies include conferences, literature
searches and training projects as research involving children, while others
use a narrower definition, referring only to projects involving children
directly as subjects. Thus, the data are not compatible.
Of the numerous departments and agencies conducting or supporting re-
search with children, DHEW supports the largest amount (see pages 38 and 39).
Within DHEW, the largest dollar amount for biomedical research involving
children is provided by the National Institutes of Health; the largest
amount of nonbiomedical research supported by DHEW is funded by the Educa- .
tion Division. Although the National Institute of Child Health and Human
Development (NICHD) is identified most closely with research on children,
virtually all the institutes have research programs that directly involve
them.
Much of the research conducted and supported by NICHD, in contrast to
the categorical disease institutes, involves the study of normal and abnormal
27
physical, cognitive, behavioral and social development. Examples of such
research include studies of normal and abnormal development of cellular
immunity, developmental pharmacology research to identify age-related
changes in metabolism of endogenous substances and drugs by infants and
children, evaluations of mental development of malnourished children,
attempts to develop or improve methods for predicting mature stature from
assessment of skeletal maturity at various ages, analyses of learning
patterns of children and the impact of preschool educational experiences,
intense studies of acquisition and development of language skills, and
studies of the relation of parental authority style to development of
responsibility and independence in children. Other research focuses on
determining the causes and prevention of such conditions as mental retarda-
tion, the sudden infant death syndrome, low birth weight, and accidents. Re-
search of this type supported by NICHD has included evaluation of the effects
of differing types of intervention on mental retardation associated with mal-
nutrition, attempts to prevent mental retardation in children of retarded
mothers by infant stimulation and developmental programs, development of
continuous positive airway pressure ventilation as treatment for newborns
with respiratory distress syndrome, studies of the incidence of congenital
infections in newborn infants and their role as a cause of low birth weight
and mental retardation or death, and assessments of the relation of sleep
disturbance or cardio-respiratory dysfunction as well as viral infection
to the sudden infant death syndrome.
Research supported by the National Institute of Dental Research and
involving children consists primarily of clinical trials, usually in schools,
28
of techniques to reduce tooth decay. Such techniques include fluoride
inouthrinses, mechanical plaque removal from teeth, and sealants. Other
studies range from those involving children only as sources of biologic
materials for study (saliva, plaque), or comparing behavioral responses
to an initial visit to the dentist after various means of orientation
and preparation, to developing new surgical and orthodontic rehabilita-
tive procedures for cleft palate and other craniofacial birth defects.
Examples of child research supported by the National Institute of
General Medical Sciences include follow-up studies of children given vari-
ous drugs as newborns or whose mothers received certain drugs during preg-
nancy, developing new methods of instrumentation for procedures such as
cardiac catheterization, devising noninvasive techniques of sampling or
monitoring (salivary drug levels, skin oxygen electrode), and conducting
eye exams and constructing pedigrees to ascertain the genetics of refrac-
tive errors.
The focus of research involving children that is conducted and supported
by the National Institute of Neurological and Communicative Disorders and
Stroke is on perinatal factors associated with cerebral palsy and mental re-
tardation, discovering the enzymatic basis of hereditary disorders of the
nervous system and in certain instances attempting enzyme replacement therapy,
and determining the causes and evaluating treatments of such conditions as
learning disability, dyslexia, stuttering and aphasia. Children are also
involved with adults in NINCDS studies of the etiology and treatment of the
various epilepsies, investigations of slow virus infections of the central
29
nervous system, management of spinal cord injuries, and development of im-
proved sensory aids for the handicapped.
The National Cancer Institute does not target its programs toward
children as a group, but many children are included in the research proto-
cols for particular cancers. The research involves testing of various thera-
pies to develop improved treatment, and evaluating new diagnostic methods.
■ The National Eye Institute conducts and supports a number of studies of
eye disorders involving children. These include evaluation of medical and
surgical treatments for congenital and juvenile glaucoma, development of im-
proved diagnostic procedures for juvenile macular degeneration and retinitis
pigmentosa, use of new techniques to evaluate eye movements, use of color TV
for color vision screening, and research on the perceptual components of
reading.
A large number of studies of the National Heart, Lung and Blood Insti-
tute involve children. Some involve minor intervention, such as studies of
blood pressure and blood lipids in large populations of school children to
obtain information on prevalence of hypertension and of certain risk factors
(hyperl ipidemia) . Other noninterventional studies include evaluating risk
factors in children whose parents have heart disease, obtaining longitudinal
information on blood pressure determinations of children, and studying the
long term natural history of congenital heart defects by following the status
of children with the defects over many years. The Institute also supports
studies of effective therapy for pediatric lung disorders, including respira-
tory distress syndrome, cystic fibrosis, and bronchiolitis. Blood disorder
30
research involving children includes study of Factor VIII inhibitors in
hemophilia (using a sample of the child's blood obtained at routine clinic
visits), recording the incidence and source of infection in children with
sickle cell disease, assessing the mental and emotional development of
children with sickle cell disease, recording sexual maturation of sickle
cell patients compared to their unaffected siblings, identifying the effects
of a tutoring program on school attendance and performance of sickle cell
patients, and evaluation of prophylactic penicillin to reduce the incidence
of infection in patients with sickle cell disease.
Children's research programs supported by the National Institute of
Allergy and Infectious Diseases focus on asthma and allergic conditions,
immunodeficiency states, and infectious diseases. Included in the broad
range of activities are studies designed to develop or improve tests to
specifically diagnose allergy to various agents at different ages; a double-
blind clinical trial of use of transfer factor as therapy for certain immuno-
deficiency states; development and clinical testing in infants and children
of vaccines against Hemophilus influenza type B, meningococcus, pneumococcus,
streptococcus, and several viruses; identification from stool samples of the
virus responsible for a large portion of the cases of infant diarrhea; and
epidemiologic studies of a wide variety of infections. ,
Children are usually involved with adults in studies of the National
Institute of Arthritis, Metabolism, and Digestive Diseases, although some
of the disorders studied (such as juvenile rheumatoid arthritis or juvenile
diabetes) strike first during childhood. Examples of the studies which
31
include children are comparisons of new drugs or various schedules of admin-
istration in treating lupus nephritis, evaluation of dietary modification
as therapy for certain genetic defects (such as galactosemia) or for uremia
or deficiency diseases, comparison of growth and sexual development as well
as psychosocial function with peritoneal dialysis as opposed to hemodialysis
in chronic renal failure, and evaluation of the physical and behavioral ef-
fects of hypertransfusion to maintain hemoglobin level at 12 grams rather
than 9 grams in patients with Cooley's anemia.
The National Institute of Environmental Health Sciences supports a
variety of research on methods of diagnosing, treating and preventing lead
poisoning in children, as well as the extent and consequences of the condi-
tion. Similar types of studies are supported for other environmental
hazards, such as mercury, cadmium, sulfur dioxide, and various pollutants.
These studies involve such procedures as developing assays to measure lead
in one drop of blood or one hair and applying them in large screening pro-
grams, developing and studying the effects of various treatments to remove
lead from the body, correlating lead levels in shed teeth with neuropsy-
chologic test performance of children, or longitudinal testing of pulmonary
function of school children in cities with different levels of pollutants.
A number of epidemiologic studies have examined the relation of such factors
as prenatal x-ray exposure to the development of childhood cancer, pesticide
exposure to chromosome damage, or exposure to various known toxins to mental
retardation.
32
The Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA),
through its three component institutes (NIMH, NIDA, NIAAA), serves as
the focus of DHEW behavioral research, although many of its activities
are biomedical as well. The National Institute of Mental Health con-
ducts or supports studies of developmental processes of the child and
the family, child abuse, early diagnosis of dysfunction, and interven-
tion programs to promote healthy emotional and cognitive growth. Exam-
ples include longitudinal studies of mother-infant interactions, studies
of the effect of obstetric medication on infant perceptual functioning,
effects of maternal behavior on infant learning, behavioral identifica-
tion of the hyperkinetic syndrome, effects of methyl phenidate and amphet-
amine on hyperactive children and their influence on urinary dopamine
metabolites, genetic studies of the offspring of schizophrenics, studies
of the delivery of psychiatric screening and services to children, and
investigation of factors contributing to juvenile delinquency.
The National Institute on Drug Abuse targets a significant portion
of its research program toward children. Much of this research involves
development and evaluation of education programs for children regarding
drug abuse, with special attention to appealing to elementary school
children and minorities. Other research involves study of attitudes
among children toward drug use, investigation of the extent of drug use
by children, and assessment of the effects of maternal narcotic addictior
on the fetus and newborn infant. Studies comparing various treatment
methods and the efficacy of treatment for the young drug abuser are also
supported.
33
The National Institute on Alcohol Abuse and Alcoholism supports some
research involving children. These projects generally involve experimental
education programs for children on alcohol use and abuse, study of the
social and cultural antecedents of alcoholism, evaluation of treatment
programs for the very young alcoholic, studies of the effects of maternal
alcohol use during pregnancy on the newborn and on family health, and sur-
veys of the nature and extent of alcohol use among children of various ages
and socioeconomic groups.
Other agencies within the Public Health Service also conduct or sup-
port research involving children. Although its primary mission is providing
health services, the Maternal and Child Health Service of the Bureau of Com-
munity Health Services, Health Services Administration, devotes considerable
effort to research related to its programs. In addition to studies of preg-
nancy and childbirth, the MCHS supports studies of means of improving patient
compliance with physicians' directions, the impact of improved health insurance
coverage of maternity care on infant mortality, disability outcomes for child-
hood amputees, using a trained mother as therapist in cerebral palsy therapy,
and numerous evaluations of MCHS programs and projects. The largest portion
of research involving children that is conducted or supported by the Center
for Disease Control is the development, testing, and evaluation of vaccines.
Epidemiologic studies of the CDC often involve children, such as in studies
of the incidence of childhood cancer in relation to arsenic levels near a
smelter, or analysis of interpersonal contacts among patients with Hodgkin's
disease as a possible factor in its epidemiology. Surveillance activities
34
may involve children, as in the study indicating that an outbreak of Reye's
syndrome closely followed an epidemic of influenza B virus infections, and
in the birth defects monitoring program (which involves children only by
utilizing newborn infants' hospital discharge summaries). Within the Food
and Drug Administration, the Bureau of Biologies supports some research in-
volving testing of vaccines in children; pharmaceutical testing in children
is regulated but not conducted or supported by the FDA. , ■ '
Some DHEW components outside the Public Health Service also conduct
or support research involving children. Three divisions of the Office
of Human Development (Office of Child Development, Office of Youth Develop-
ment, and Rehabilitation Services Administration) have child research pro-
grams. Research in the OCD Head Start program includes studies of the
effects of different ratios of caregivers to children in child care centers,
evaluation of progress made by children in different types of Head Start
programs, and analysis of a family oriented "Home Start" program in rural
areas. OCD also supports studies related to determining causes of child
abuse and neglect and developing intervention programs to assist parents
of such children, studies of attempts to improve the interface of parents
with schools and social institutions to assist the developing child, and
research on the impact of residential institutional experiences on child
development. The research supported by OYD focuses on analysis of causes
and various support services for runaway youths. The RSA supports research
on rehabilitative techniques for children with cerebral palsy, mental retarda-
tion, or other disabling conditions.
35
Another DHEW component, the Social and Rehabilitation Service, sup-
ports research with children related to child welfare services, child
support, and health services. Studies involve developing methods to
identify early warning signals of child abuse and neglect, assessing the
cost-effectiveness of different types of day care, developing alternative
approaches to foster care and adoptions, evaluation of income maintenance
programs and their effect on children, assessing the impact of family
planning services on reducing the number of unwanted births (especially
to teenagers), and evaluating the cost-effectiveness of various methods
of providing Early and Periodic Screening, Diagnosis and Treatment ser-
vices. (In 1977 a departmental reorganization abolished the Social and
Rehabilitation Service, and most of its programs have been transferred to
the Office of Human Development or the Health Care Financing Administra-
tion.) '
The largest amount of research involving children in DHEW, both in
terms of funds and number of projects, is conducted and supported by the
Office of Education and the National Institute of Education. This re-
search is intended to improve the quality of education by developing and
demonstrating the effectiveness of new approaches to education. To the
extent that changes in education techniques or practices are considered
behavior research, these activities fall within the mandate of the Com-
mission. Examples of the types of research supported include studies of
the multiunit school system as a means to reorganize elementary schools
to provide more individual attention, evaluation of a program combining
36
on-the-job experience with academic learning, developing improved methods
for acquisition of basic skills as well as better means to assess achieve-
ment, evaluation of various primary education programs (Project Follow
Through) for their ability to maintain gains achieved by children in Pro-
ject Head Start, developing improved techniques for early childhood edu-
cation and teaching handicapped children, and research in the Right-To-
Read program designed to develop effective remediation procedures for .
children who are functionally illiterate.
Departments of the federal government other than DHEW also conduct
or support research involving children. The Department of Agriculture
supports research through land grant institutions and the Agriculture
Extension Service on childhood nutrition and growth, education, and
child development. The Department of Justice, through the Law Enforce-
ment Assistance Administration and its Office of Juvenile Justice and
Delinquency Prevention, conducts and supports research relating to juve-
nile delinquency and rehabilitation of young offenders. The Department
of Labor supports experimental programs to improve vocational education
and job opportunities for adolescents, with emphasis on minorities, the
disadvantaged and the handicapped. Finally, physicians and other person-
nel in the military hospitals of the Department of Defense conduct a wide
variety of biomedical and behavioral research involving children.
Figures 1 and 2 show the number and proportion of federally sponsored
research projects supported by the various departments and agencies.
37
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39
Chapter 3, Survey of Review and Consent Procedures
Information about informed consent, risks and benefits, and review
procedures in research involving children was obtained in the Commission's
larger survey of review and consent procedures for research involving human
subjects. The survey, which was conducted under the direction of Robert A.
Cooke, Ph.D., and Arnold S. Tannenbaum, Ph.D., of the Survey Research Center
at the University of Michigan, focused on review procedures and research at
a probability sample of 61 institutions drawn from the more than 420 insti-
tutions with Institutional Review Boards (IRBs) approved by DHEW.* Research
projects in which more than 25 percent of the subjects were children consti-
tuted more than one-fourth of all projects approved by sample IRBs during
the period under study, July 1974 to June 1975. The Survey Research Center's
report on research involving children was based primarily on interviews with
471 investigators whose research involved children, analyses of consent forms
used in this research, and interviews with 144 subjects or third parties who
consented on their behalf.
Research involving children was reviewed in many types of institutions,
most frequently in medical schools (almost half of the research) and to a
lesser extent in universities, hospitals, and institutions for the mentally
retarded and mentally ill. Overall, slightly more biomedical than behavioral
research involving children was conducted. In most of the biomedical research
* The study was confined to institutions from which DHEW had accepted a
"general assurance" of compliance with DHEW regulations for protection
of human subjects.
41
projects involving children, the subjects were identified by investigators
as patients with diseases to which the research was related. The most com-
mon biomedical studies involved drug administration or examination of tissue
or bodily fluids. Subjects in behavioral research were selected most fre-
quently because of a behavioral or educational problem they were experiencing.
Most of the behavioral research involved observation, testing, interviews or
questionnaires; about one-fourth of the behavioral research involved the
study of a behavioral intervention. ■ • • '
Risks and benefits of research involving children . Investigators pro-
vided assessments of the probability and magnitude of the risks and benefits
of their research. Most risks to subjects were described as pertaining to
minor psychological stress, embarrassment, or minor medical complications,
and most risks were indicated to be of a "very low" probability. Higher
probabilities of medical or psychological harm were reported in only about
five percent of the studies involving children. • .
In analyzing investigators' responses to questions regarding risk,
studies expected to benefit subjects were compared to studies not expected
to benefit subjects. Projects expected to benefit subjects were defined
as those which were reported (a) to be conducted for the primary purpose
of benefiting subjects or (b) to have a medium or high probability of
benefiting subjects. So defined, these "beneficial projects" made up 57
percent of the total.
Investigators' assessments of the probability of psychological stress
or medical complications were substantially lower for research not expected
42
to benefit subjects. For example, in studies expected to benefit subjects,
investigators reported a very low probability of "serious medical compli- ..
cations" in 18 percent of the studies, and a higher probability in an addi-
tional five percent of the studies. In studies not expected to benefit sub-
jects, comparable figures for the risk of serious medical complications were
six percent and zero percent. The only risks for which there was no dif-
ference between these types of studies were those in which a breach in con-
fidentiality might result in embarrassment (a factor in about one-fourth of
all studies involving children, usually at a "\/ery low" probability) or in
legal jeopardy (a factor in about 10 percent of all studies, usually at a
"very low" probability).
Informed consent .* IRBs showed considerable concern with informed con-
sent in their review of proposed research involving children. About one-
fourth of the investigators doing research with children reported that their :
IRB had requested changes in the way consent would be obtained in their studies.
Almost all of these changes pertained to the content of consent forms rather
than to the setting or circumstances under which consent would be obtained.
Consent modifications were requested most frequently in projects that in-
volved the secondary use of materials gathered for other purposes; the most
common consent change in such research was the requirement that consent be
* Because the terms "consent of children" and "third-party consent" were
used in the survey, they appear in this section. As is explained in the
Commission's recommendations, the Commission has generally referred to
the "assent" of children in order to distinguish this from the legally
effective informed consent that an adult can give, and to third-party
"permission," which it believes to be a more accurate term than third-
party "consent."
43
documented in writing rather than obtained orally. Anrong other biomedical
and behavioral projects, the most common consent change was the addition of
materials to consent forms.
Oral or written consent was sought in almost all projects in which
children participated, the exceptions being projects involving question-
naires (where the return of the questionnaire was seen as implying consent),
routine treatment, or research presenting no risk. In almost all projects
from children's hospitals and about two-thirds of the projects from other
settings, investigators requested consent from third parties, usually from
parents, relatives or legal guardians. Most investigators felt that such
involvement of third parties protected subjects "very well" or "fairly well,"
but a small number indicated otherwise. The median age of subjects above
which no consent was obtained from a third party was 18 years of age, while
the median age below which consent was not obtained from subjects, in addi-
tion to third-party consent, was seven years of age.
Written consent forms were used in almost all research in children's
hospitals and in about three-fourths of the projects in other institutions.
Oral consent, without consent forms, occurred most frequently in behavioral
research (18 percent), but also occurred in seven percent of biomedical
studies. About 10 percent of the behavioral researchers and two percent
of the biomedical researchers reported that consent forms were used in
their studies, but that no oral explanation was provided.
The consent forms themselves were frequently incomplete in terms of
six consent elements mentioned in DHEW regulations (45 CFR 46.103(c)) ~
44
the purpose of the research, the procedures involved, the risks, the bene-
fits, a statement that subjects are free to withdraw from the research,
and an invitation to ask questions. Only 20 percent of the consent forms
from children's hospitals and other biomedical institutions, and only five
percent of the consent forms from other institutions, contained as many
as five of these six elements. Descriptions by investigators of the topics
covered in oral explanations added only negligibly to the report of infor-
mation transmitted to subjects.
Some elements appeared much less frequently than others in consent
forms. There was no description of the purpose of the research in 30 per-
cent of the consent forms, and no description of the research procedures
in 18 percent. Risks were not discussed in 54 percent of consent forms.
Two-thirds of these cases were in studies described by investigators as
entailing at least a very low probability of minor harm to subjects. The
benefits of the research (or absence of benefits to the subjects) were
not described in 64 percent of the consent forms; benefits to subjects
were mentioned in only one-fourth of the forms in studies which investiga-
tors described as being expected to benefit subjects. A statement regarding
withdrawal from the study was not present in 14 percent of the consent forms;
however, many of these may have been from studies in which the active
participation of subjects ended quickly. An offer to ansvjer questions
appeared in half of the consent forms. A description of alternative treat-
ments might have been expected in projects designed primarily to benefit
subjects. However, alternatives to participation in the research were not
mentioned on more than 80 percent of the consent forms in these studies.
45
The survey also showed that consent forms tend to be written in lan-
guage that may be difficult for the lay person to understand. A "reading
ease score" was computed for each consent form, using a standard measure,
the Flesch Readability Yardstick.* In spite of the review and approval
of these forms by IRBs, consent forms tended to be written in scientific
language. Descriptions of the procedures to be used in the research tended
to be somewhat more readable than descriptions of the purpose of the re-
search. But, overall, fewer than 15 percent of the consent forms were
written in language as simple as is found, e.g., in Time magazine. This
raises doubt about whether many subjects would find these consent forms
of substantial use to them in making decisions regarding participation in
research. No information is available on the degree to which the diffi-
cult language of consent forms is mitigated by oral explanations in lan-
guage more readily understood by the average lay person.
Subjects' and third parties' perceptions of research . A representa-
tive sample of subjects and third parties was not obtained, and data from
these sources must therefore be interpreted with caution. Almost three-
quarters of the respondents reported that they were given as much informa-
tion as they wanted; 19 percent said that they were given less than they
wanted. Almost all said the information was clear and understandable and
that the researchers were willing to ansv/er any questions, but 17 percent
reported that they did not understand, prior to the subject's participation.
* Rudolf Flesch, A New Readability Yardstick, Journal of Applied Psychology ,
Vol. 18, No. 3, June 1948, pp. 221-233.
46
that the subject "was to be involved in research." The most frequent reason
given for participation in a research project was some anticipated medical
or psychological benefit. Ninety-six percent of the respondents reported
no unexpected difficulties, and the four percent who did report difficulties
felt that they were not very serious. Sixty percent felt that the subject
benefited from the research. ■ -
IRB impact on proposals involving children . IRBs requested modifica-
tion in about 60 percent of the research proposals involving children,
usually during the formal review process but occasionally through informal
contacts prior to review. The most frequent modifications, occurring in
about one-third of the proposals, were for clarification or additional in-
formation. As discussed above, modifications related to informed consent
were required in one-fourth of the proposals. Changes pertaining to reduc-
tion of risk or discomfort were required in about five percent of the pro-
posals.
Investigators' attitudes toward the IRBs were, for the most part,
more favorable than unfavorable. Nonetheless, half of the investigators
offered suggestions for improvement or expressed concern about such pro-
blems as the time-consuming nature of the review process and the failure
of IRBs to discriminate between research involving high risk and research
involving minimal or no risk. Their suggestions included elimination of
parts of the review process (e.g., regarding research with minimal or no
risk or research using previously gathered materials), elimination of writ-
ten consent procedures for studies with minimal or no risk, changes in IRB
47
composition (some want more lay representation, while others want less),
and better information about the expectations of the IRB.
Summary . This survey indicated that IRBs give considerable attention
to their review of research involving children and that significant risks,
to the limited extent to which they are present in such research, are found
in studies that are expected to be of benefit to the subjects. However,
the survey also provided evidence of shortcomings in the obtaining of in-
formed consent. Although oral or written consent was generally reported to
have been obtained whenever appropriate, a small percentage of investigators
indicated that no oral explanation had been provided, and consent forms were
frequently incomplete and tended to be written in language that the lay
person might find difficult to understand. Despite this, the survey pro-
vided no indication that there is widespread dissatisfaction among children
or parents regarding their experience in research, although a significant
minority of respondents indicated that they had not understood, prior to
the subject's participation, that research was to be involved.
48
Chapter 4. Views Presented by the National Minority
Conference on Human Experimentation
In order to assure that minority viewpoints would be heard, the Commis-
sion contracted with the National Urban Coalition to organize a conference
on human experimentation. The conference was held on January 6-8, 1976, at
the Sheraton Conference Center, Reston, Virginia. Attended by over 200
representatives, it provided a format for presentations of papers and work-
shop discussions from which a set of recommendations emerged. Two sections
of the Minority Conference focused on children as research subjects.
Henry W. Foster, Jr., M.D ., in a background paper, suggested that chil-
dren not be excluded from participation in "nontherapeutic" research, since
"there clearly exists the need to continue the search for better therapies
and cures for the many childhood diseases that are so prevalent and devasta-
ting." However, he urged that a proper balance between risks and benefits
be maintained, and that definitions of childhood take into account social
and ethnic differences in age of maturation. He recommended that parental
consent for the participation of children in research be accepted as legally
and ethically valid, and that no socio-economic groups participate dispro-
portionately as research subjects.
Crystal A. Kuykendall. Ph.D ., spoke about institutionalized children,
emphasizing the disproportionate numbers of minority children who are
labeled mentally retarded or mentally disabled and placed in institutions.
She indicated that these children are most vulnerable to the effects of in-
stitutionalization. Citing a 1975 study on the Futures of Children, by
49
Vanderbilt University, she noted that there are currently 200,000 indi-
viduals in public institutions who are diagnosed as mentally retarded,
and thirty percent of these are children. She urged the development of
alternatives to institutionalization for all but the most severely disa-
bled individuals, better criteria for diagnosis, and better educational
methods to develop the capacities of each person as fully as possible.
The Conference Workshops on Children submitted recommendations which
included: (1) a prohibition of the exploitation of any one segment of the
child population; (2) an exclusion of institutionalized children from re-
search, except that which is designed to improve their conditions; (3) a
prohibition of the use of psychosurgery on children; (4) the consent of a
children's advocate in addition to that of parents; and (5) the consent of
children over age seven when their participation in "nontherapeutic" re-
search is solicited.
50
Chapter 5. Views Presented at Public Hearings
On April 9, 1976, the Commission conducted a public hearing on the
issue of research involving children. Summaries of the testimony follow.
William Charlesworth, Ph.D. and Julius Richmond, M.D . (Society for
Research in Child Development) presented the results of a survey in which
a sample of the Society's members were polled regarding their research
practices. The sample included investigators involved in a wide variety
of pediatric research, although it is almost entirely behavioral rather
than biomedical. A majority of the investigators were funded by DHEW or
other federal agencies. All of the investigators reported that they fol-
lowed a specific code of ethics, and 80% reported that their research is
reviewed by an ethics committee. Ninety-six percent reported that they
had worked at one time with normal subjects, 31% had worked with handicapped
or retarded subjects, and 25% had worked with institutionalized persons.
A third of those studying preschoolers obtained consent from the chil-
dren as well as from parents (or, in a very few cases, from school officials).
From that age group on, there was a greater tendency to obtain consent from
the subjects. Eighty-three percent mentioned that they informed the sub-
jects that they may refuse to participate or withdraw from the study at any
point without prejudice. Deception was employed by 23% of the investigators
if they felt it necessary for research purposes, and approximately 40% re-
ported that they used various kinds of inducements or compensation to per-
suade or reward subjects or parents to participate in the research. (The offer
of compensation for participating is often viewed as an inducement to persuade.)
51
Respondents were asked to answer questions about risks involved in
their own studies and to identify any occurrences of injury. Physical
risks were a possibility in only four of the 3,400 studies represented in
the sample, and psychological/social risks were reported in less than 2%
of the sample (60 studies). None of the physical risks led to any known
undesirable consequences, but in about 13 cases, subjects reportedly ex-
perienced some consequences of the psychological/social risks, most of
which appeared to be short-term. Thus, in only 1/4 of 1% of the 3,400
studies were children placed at any risk, and no serious or long-term in-
jury was reported. The questionnaire also inquired about the risks posed
by studies not conducted by the respondents but about which they had first-
hand knowledge. The survey revealed that 9 respondents were familiar with
a total of 16 studies involving some sort of physical risk and with 173
studies involving psychological/social risk. Dr. Charlesworth believes
that this survey indicates that the overwhelming majority of investigators
maintain a high level of research ethics. The Society recommends that the
potential dangers involved in the use of deception (e.g., the child's losing
trust in adults) be studied further, that there be increased education about
the importance of research ethics, that review procedures be improved and
that, if necessary, professional sanctions be invoked in cases of proven
violations.
Edward F, Zigler, Ph.D . (Division of Developmental Psychology, American
Psychological Association) suggested that investigators should educate the
public about the nature and benefits of behavioral studies involving children
52
in order to dispel suspicion and distrust. In addition, they should develop
enlightened informed consent procedures which respect the child's wishes as
much as possible, although Dr. Zigler acknowledged that it is difficult to
determine when a child is possessed of sufficient understanding that he or
she should be consulted. He urged that investigators turn their attention
more frequently to applied science to enrich both the theoretical structure
of their field and the quality of life in our society. He further suggested
that the Commission develop guidelines which protect both the rights of sub-
jects and the rights of behavioral scientists, so that the latter may continue
their exploration of human behavior. Should the task of the behavioral scien-
tist ever become impossible, the ultimate loser will be society. Dr. Zigler
believes that increased parent involvement in the research process, especially
in institutional settings, is a crucial step in resolving the problems of
distrust which, he believes, threaten research activities.
Frank Oski, M.D . (Society for Pediatric Research) presenting the testi-
mony of Frederick C. Battaglia, M.D., described a variety of major contri-
butions arising from pediatric research. He urged the Commission not to try
to distinguish, in all cases, between "therapeutic" and "nontherapeutic" re-
search, but rather, to focus on evaluation of risks. He suggested that the -
proper protection of children involved in long-term studies of development,
maturation and aging could be accomplished without a cumbersome review mecha-
nism. In cases where child abuse is present or likely, however, as well as
in adoption and juvenile delinquency programs, he suggested there may be a
need for an advocacy system. Dr. Battaglia expressed concern that the
53
government's continued diversion of training funds from research to primary
care will further reduce the pool of investigators who may be best qualified
to judge the merits of research involving children. He suggested two review
mechanisms: (1) for "therapeutic" research protocols where "parenting" is
adequate and parental consent appropriate, the review should be conducted
by the IRB which should include experts in pediatrics and child psychiatry;
(2) for all "nontherapeutic" research protocals and any "therapeutic" re-
search where the question of adequate "parenting" is raised, an "Ethical
Review Group" at NIH would be responsible for review and no local review
would be required. In no case should the investigator also serve as the
child's physician. Long-term studies requiring normal controls and involv-
ing procedures of minimal risk should be permitted without burdensome review.
Alvin M. Mauer, M.D . (St. Jude's Children's Research Hospital) testi-
fied primarily about research involving children with cancer. He empha-
sized the importance of random assignment of children to different treat-
ment programs in order to evaluate the efficacy of the new therapies.
Further, he views the random assignment of subjects as preferable to asking
parents to choose which treatment their child should have. Dr. Mauer warned
that if local protection committees are required to review each patient's
consent form, committee review might become a rubber stamp operation. In
addition, he prefers local review to national review since IRB members are
closer to the issues and bureaucratic problems are avoided. The consent of
both parents should not always be required for "therapeutic" research, nor
should a child's formal consent be a prerequisite for all "therapeutic" research
54
procedures. Dr. Mauer proposed that about five percent of the children and
parents involved in a particular research protocol be questioned to determine
whether they understood the consent forms.
Sheridan Neimark, Esq . (National Society for Autistic Children) indi-
cated that the Society is deeply concerned that federal legislation may in-
hibit research of potential benefit to children and severely impaired
I
adults. They believe that existing regulations are sufficient and suggest
that certain provisions be reconsidered (e.g., requiring incompetent chil-
dren and both parents to consent to a research protocol ) . The consent of
both parents should not be required if one parent has legal custody or if
the other parent cannot be located after a reasonable effort has been made.
While the Society does not approve of the use of patients as research sub-
jects before appropriate or adequate animal studies have been conducted, it
believes that careful and discriminating investigators should be supported.
Studies involving high-risk drugs should be permitted as long as there is ■
strong evidence that they may benefit the patient. Parents should have the
option of vetoing their child's participation in any research they feel would
be detrimental. Information on the risks, benefits, and any known side ef-
fects of experimental programs should be provided whether or not the parents
request such information; and parents should be free to refuse their child's
participation in any experiments which are not an integral part of their
overall treatment program without prejudice.
Bertrand G. Winsberg, M.D . (State of New York Department of Mental Hygiene)
I expressed his concern about two major issues: minority group participation in
55
research and the appropriateness of obtaining informed consent from children.
He stated that the assertion that the poor and ethnic minorities are being
exploited by researchers has only partial validity. Much of the research
data collected from these populations contributed significantly to their
health care and, in many instances, only to theirs (e.g., nutrition studies).
To inhibit research involving minorities will reduce the quality of resources
and services available to them, and to restrict "nontherapeutic" research will
handicap efforts to understand the nature of many disease processes. Dr.
Winsberg sees no way in which to present research protocols to children so
that meaningful consent can be obtained; in addition, he believes that sub-
jecting children with physical or behavioral disabilities to such consent
procedures may be harmful since it would expose them to requests which char-
acterize them as abnormal. He further believes that the biomedical research
establishment could be regulated effectively, like any other business, through
federal and state agencies, although he would like to avoid a complex and
unworkable bureaucracy- In the last analysis, he said, various responsible
and knowledgeable agents of society must determine whether the risks and dis-
comforts of any procedure are justified in the case of given children, taking .
into consideration the needs of both the research subject and the social sys-
tem. Finally, Dr. Winsberg urged that a mechanism be incorporated in any
new regulation to assess its effectiveness. In response to a question. Dr.
Winsberg indicated that he viewed the problem of distinguishing between
"therapeutic" and "nontherapeutic" research as insoluble.
Norman Kretchmer, M.D., Ph.D . (National Institute of Child Health and
Human Development) stated that since any biological or behavioral event which
56
occurs in children is intertwined with their growth and development, two
conclusions follow: (1) children must be studied in order to advance
pediatric medicine, and (2) the long-term effects of any procedures which
are performed on a child must be considered. Dr. Kretchmer offered the fol-
lowing recommendations: (1) children with no natural or adoptive parents,
children detained by court order in a residential facility, and institu-
tionalized handicapped children should be excluded from participation in
"nontherapeutic" research involving risk; (2) a list of clinical procedures
deemed to be without risk (e.g., collecting blood, urine and stool samples)
should be exempted from the review process, but not from the informed con-
sent requirement; (3) minors should be given the opportunity to refuse to
participate in "nontherapeutic" research, and such a refusal should be
honored (children might be more inclined to express their fears or objec- .
tions to research if placed in a discussion group of three or four peers);
and (4) panels reviewing protocols involving the use of children should in-
clude among their members a child advocate from outside the research community.
It is extremely important, he added, that parents participate in the research
process on a continuing basis. *
Jean A. Cortner, M.D . (Association of Medical School Pediatric Chairmen)
described many advances in pediatric care which have reduced infant mortality
and profoundly affected child health. Dr. Cortner believes that basic and
applied research are both necessary and should not compete with each other.
A middle ground must be cultivated between children's right to a better tomor-
row (through the acquisition of new knowledge) and their right to a safe today.
57
Dr. Cortner believes that safety can be assured through proper peer review.
Since young children cannot give informed consent, their parents or guar-
dians, who bear responsibility for their welfare, must give consent. Re-
search which will place children at unnecessary risk must not be allowed,
but research which promises to improve the health of everyone should be
encouraged.
Elizabeth J. Levinson, Ph.D . (Psychologist, Orono, Maine) expressed
concern about three issues: (1) the "Buckley law" which places restrictions
on the release of data from school records to outsiders, (2) the entry into
these records of certain types of data, and (3) restrictions on the adminis-
tration of tests to children without "fully informed" parental consent.
These restrictions conflict with state laws requiring that children be
evaluated to determine the presence or absence of certain handicaps and
they interfere with the research aims of the Office of Child Development
and the National Center on Child Abuse and Neglect. Dr. Levinson has found
that parents who abuse their children, who are emotionally unstable or are
mentally retarded, are least likely to consent to studies of family inter-
actions, I.Q., or psychological status. By informing the parents, the chil-
dren, or both, of the purpose of such studies, there is a real danger of
introducing anxieties and other harmful effects. Hence, there is an urgent
need to modify the disclosure requirements for such research projects. Dr.
Levinson suggested obtaining informed consent from the parents but not neces-
sarily providing them with a full description of the study. She suggested
further that giving parents complete control over their children and an al-
most absolute right to privacy appears to be based on an assumption either
58
that all parents are good and wise or that children have no rights. Dr.
Levinson has discovered, however, that some parents are unwise and may
invoke privacy to veil child abuse and neglect. She urged the Commis-
sion to resolve this conflict between the rights of parents and the rights
of children.
Mr. Robert A. Bogorff (Candlel ighters. South Florida Chapter) explained
that the Candlelighters are especially interested in pediatric cancer re-
search. They advocate careful monitoring of institutional review committees
and suggest the IRB composition include more nonbiomedical members. Both
the chairman and co-chairman of these committees should be required to demon-
strate their knowledge of policies and laws regulating research. Further,
since patients' advocates are essential and must be free to devote as much
time as necessary to their duties, the Candlelighters recommend that fund-
ing agencies provide salaries for them. They should be well read in medi-
cine, law and ethics and be able to work on a professional, full-time basis.
They believe further that it is unrealistic to assume that parents of young
cancer patients will comprehend a full statement of research procedures
after one reading, while surrounded by hospital personnel and by other
family members under similar stress. Rather, they say "parents will sign
anything when confronted with cancer." They question the prevailing prac-
tice of random assignment to treatment groups and urge the Commission to
give careful consideration to this problem. Finally, they are concerned
about the inherent conflict in the doctor's dual role of physician/investi-
i gator, and about the lack of provisions for compensation for injury.
59
Joseph A. Bellanti", M.D . (American Pediatric Society) stressed the
importance of research involving children for improving pediatric medi-
cine, the distinction between "therapeutic" and "nontherapeutic" research
in children, the varying levels of potential risk in "nontherapeutic" re-
search in children, the role of the child and the parent in the consent
process, and the equitable allocation of the risks and benefits of research.
Dr. Bellanti suggested that children should be involved as much as possible
with the consent process depending upon their level of understanding. A
child's refusal to participate in a "therapeutic" procedure need not be
respected if the parents or the courts are in disagreement, but for "non-
therapeutic" research, the child's wishes should govern. He recommended
that a detailed description of the research protocol be given to the parents
and that the results of investigations be made available to them unless they
specifically request not to be told. To avoid conflicts of interest when
the attending physician is part of the research team, someone else should
be prepared to serve as the child's and parent's advocate.
George G. Graham, M.D . (American Institute of Nutrition) noted that our
knowledge of pediatric nutrition is limited, and we lack even a definition
of desirable growth rates for infants and children. Most of our knowledge
about nutrition derives from research with animals; at some point, it must
be confirmed in humans. Well over 50% of all nutritional research is con-
ducted outside of the United States, primarily because in poor countries
the question is one of survival. In this country, however, evidence is in-
creasing that infant and child feeding practices may influence degenerative
60
vascular disorders and other diseases which occur in adults. Longitudinal
nutritional studies involving normal infants and children must be conducted
if progress is to be made in determining proper levels of nutrients and
ideal growth rates, or in developing alternative ways of meeting nutri-
tional requirements which can be proven safe for children of varying ages,
health status and heredity. Subjects of nutrition research should be fol-
lowed for as long as one's resources permit; and nutritional supplements
should not be withdrawn abruptly at the end of a research project. (This
is a major source of concern when conducting research on food supplements
in impoverished areas.) Dr. Graham was not aware of any experimental feed-
ing programs for the institutionalized mentally retarded, though there have
been studies correlating nutrient intakes with the development of institu-
tionalized children. Generally, institutions are not desirable sites for
these studies. Negotiations for conducting research overseas generally
involve community representatives.
Richard B. Stuart, D.S.M . (Association for Advancement of Behavior
Therapy) spoke about behavior therapy ana the development of innovative
services for youth. Generally, these programs utilize the least intrusive
technology available to enhance social functioning. According to Dr. Stuart,
if research means monitoring the effect of an intervention, then behavioral
research and therapy are indistinguishable. He identified three stages of
research: (1) the evaluation of existing services; (2) the development of
innovative methods; and (3) the lar^e scale testing of methods which have
withstood developmental evaluation. The omission of any stage, he said.
61
would seriously hinder proper delivery of services. Dr. Stuart recommended
that research be founded upon an explicit contract between the investigator
and the participant, and he took the view that parents have the right to
offer informed consent on behalf of their children. The point at which chil-
dren are able to act as their own agents is difficult to define. Requiring
participants to give written answers to questions about the research is one
method suggested for determining the adequacy of informed consent. Dr.
Stuart urged the Commission to endorse the following principles: (1) that
all children have the right to carefully evaluated programs; (2) that chil-
dren must have the opportunity to participate in the development and evalua-
tion of programs of which they are the beneficiaries; and (3) that the rights
of children as research participants can be protected through the develop-
ment of precise standards which are strengthened by the addition of be-
havioral tests of compliance. .
Marvin Cornblath, M.D . (The Endocrine Society) stated that advances in
pediatric endocrinology and metabolism depend upon knowledge of normal values;
this requires the study of normal infants and children. The goal of research
must include discovering the etiology of diseases in order to prevent them.
Dr. Cornblath urged that a subcommittee of the IRB should monitor all research
involving children and that it should include child advocates among its mem-
bers. Further, he recommended that consent of one parent be deemed adequate,
and suggested that review boards develop a sliding scale for consent based
on the age of subjects and the procedures involved. He noted that the parents
have the final say about their child's participation in research, but that
62
the protocol should be fully explained to the child. Any effort to establish
a specific age of discretion would be unnecessarily restrictive. He questioned
the morality of depriving infants and children of the potential benefits of
well supervised and controlled clinical research.
Sanford Cohen, M.D . (American Academy of Pediatrics) stated that reliance
upon pharmacological data obtained in animal models and adults has been proven
inadequate; further, infants and children must participate in the testing of
drugs because adult counterparts to pediatric conditions do not always exist.
The Academy believes that clinical investigations in pediatric pharmacology
must continue, but under stringent requirements for review and monitoring.
Studies should not be conducted, even if they entail minimal risk, if no bene-
fits are anticipated. If "nontherapeutic" investigations are to be conducted
in children, only agents that are generally regarded as safe in the dose to
be administered should be used; further, if such studies involve pain or dis-
comfort in excess of that associated with usual hospital procedures or clinic
visits, they should be done only in children mature enough to offer their own
consent (in addition to that obtained from their parents or guardians). In
general, when children are conscious and neurological ly competent, consent
should be obtained from those who have reached the age of thirteen; and
assent should be obtained from children aged seven or older after their legal
guardian has consented but before the child is enrolled in the study. Dr.
Cohen supported the inclusion of patient advocates on the review committee.
James J. Gallagher, Ph.D . (Frank Porter Graham Child Development Center)
highlighted three major research issues: confidentiality, informed consent ■
63
and the protection from harm and exploitation. He urged the inclusion of
child advocates along with members of the public on institutional review
committees. IRBs should have unrestricted access to records and the power
to approve or disapprove research on institutionalized children. In addi-
tion, parents should be continuously involved in the consent process, parti-
cularly if their child is institutionalized. Dr. Gallagher believes that
observing normal procedures (e.g., observing interactions in a classroom)
is not an intervention requiring informed consent. Dr. Gallagher empha-
sized the great risks in severely restricting research, urging that future
generations have the right to a better chance for full growth and normal
development.
Annina M. Mitchell, Esq . (Michigan Legal Services) charged that institu-
tionalized children are exploited for research purposes (especially by drug
companies) because they are cheap, accessible and out of the public's eye.
Her position is that institutionalized minors cannot constitutionally be
used as subjects in biomedical or behavioral experimentation because the
politics of institutionalization preclude valid third party consent, and the
children are in no oosition to give adequate consent because of the coercive-
ness of the institutional setting. Recently, she said, the Michigan State
Department of Mental Health adopted administrative rules which prohibit the
use of recipients of department services as subjects in medical research if
they are under 18 years old. She urged the Commission to adopt a similar
position. Ms. Mitchell is concerned that some experimentation in the name
of mental health raises the spectre of increasing classification of children
64
as deviant, and that such labeling will take its toll in later years. She
asked the Commission to impose a moratorium on research involving children '
until it can determine whether, and under what conditions, such experimenta-
tion should be sanctioned.
Judson Van Wyk, M.D. and Maria New, M.D . (The Lawson Wilkins Pediatric
Endocrine Society) stated that studies in adults or in experimental animals
are not adequate to understand, diagnose and treat abnormalities which
occur during childhood. Further, Dr. Van Wyk said, the subjects of research
benefit from their participation by receiving more attention and considera-
tion than those treated solely in a therapeutic context. He recommended
that local committees have the primary responsibility for continuing review
of research, and that they be empowered to approve no-risk projects. In
addition, a National Clinical Research Advisory Board should establish
policy and review all questionable research. Restraint should be exer-
cised before inflexible standards are imposed, for we should not exclude
children, as a class, from the benefits of new knowledge. In some instances,
he added, it is difficult to distinguish between "therapeutic" and "nonthera-
peutic" research; and often, there can be no "therapeutic" research without
"nontherapeutic" research.
Donald F. Klein, M.D . (Long Island Jewish-Hillside Medical Center) sug-
gested that the biomedical investigator cannot claim the privileges of the .
medical practitioner when research is aimed at generating new knowledge rather
than providing service. Experimentation involving nonpatients (1) should en-
tail low risk to the subject and society, (2) should be likely to benefit
65
society, and (3) should be founded upon well established procedures for experi-
mental intervention. In addition, the experimental effect should be easily
reversed and temporary, and there should be no other alternative procedure
which can yield the information. The subject or the subject's guardian
should be able to comprehend the nature of the experiment. Dr. Klein be-
lieves that the protection necessary for "therapeutic" research has been
exaggerated, especially since research often occurs under the rubric of pro-
fessional services. He suggested that the social trust in researchers could
be bolstered by certification of investigators. Institutional Review Boards
should be composed of certified investigators, along with lay members and
ethi cists, with an opportunity for appeal to a board of biomedical research.
Dr. Klein argued that to prohibit the use of sick children and the mentally
ill as experimental subjects, when no feasible alternatives are available,
is to condemn them to continued suffering. He suggested that instead of a
contract model of consent, the IRB assist in determining the appropriate
participation of children and the incompetent.
Robert Reichler, M.D . (American Academy of Child Psychiatry) believes
that when the needs of suffering individuals conflict with community prior-
ities, the individual should come first. However, this is not always the
case. He described the diversity of pediatric mental health problems in
this country to emphasize the enormity of the challenge to science, adding
that the clinician is often characterized as warm and compassionate, while
the investigator is viewed as cold and unfeeling. As a result, poor clinical
treatment is more readily tolerated than good research because it is assumed
56
that children in behavioral research projects are at a greater risk than
those receiving no treatment, or poorly evaluated drugs. Dr. Reichler
believes that obtaining fully informed consent from children is unrealis-
tic and legally impossible, whether they participate in research or in
treatment. Whenever parental protection is inadequate or unavailable,
additional review mechanisms should be invoked. When normal controls are
required for a study, and samples of substances have been obtained for
some other appropriate purpose, the samples might be utilized in such
studies if no additional burden or risk is placed on the child. The rights
of children include the right to better, safer, and more adequate treatment
as well as protection from unnecessary risks and exploitation. While addi-
tional guidelines for review committees may be useful. Dr. Reichler urged
that rigid barriers to research involving children not be imposed.' ■
Robert L. Sprague, Ph.D . (Institute for Child Behavior and Development)
urged the Commission to view research on children from the standpoint of
social costs and benefits. The parents of handicapped children often ex-
pect the development of new information and new techniques to help them with
their problems, and Dr. Sprague considers that expectation to be reasonable.
He challenged the assumption that accepted clinical practice always involves
less risk than an experimental procedure, citing several experimental pro-
grams for retarded and handicapped children which proved more beneficial than
standard practice. He urged the Commission to weigh the cost, in humanitarian
terms, of whatever regulations for human experimentation they may recommend.
67
Mrs. Gladys Kazyak (National Coalition for Children) is particularly
concerned about behavior modification programs which are offered in schools
under the guise of compulsory education. She views the school system as a
form of involuntary institutionalization, and challenged both the methodol-
ogy and objectives of behavior modification programs in such settings. In
addition, she feels that any behavioral research involving deception is dis-
honest and should be eliminated. The consent of both parents should be re-
quired, and there should be no substitutions. All research protocols should
include an evaluation of the potential effect they will have on the subjects,
and investigators should accept responsibility for the outcome of their in-
vestigations. Unethical research should be eliminated by withdrawing public
funding; ethically acceptable research should continue.
Marian R. Yarrow, Ph.D . (National Institute of Mental Health) empha-
sized the need for "nontherapeutic" behavioral research involving children.
She made four corranents about informed consent: (1) it has many levels of
meaning for different kinds of children; (2) it is a continuing process and
not a one time affair; (3) it is improper and meaningless to propose an
age at which a child may give informed consent, since there can be no single
criterion; (4) we must question the purpose of informed consent. Dr. Yarrow
suggested that the issues of informed consent are different for medical stud-
ies involving risk than for behavioral studies without risk. Occasionally,
fully informed consent may pose an additional hazard to the subject, or full
disclosure may result in biased findings. Complete parental control of the
consent process assumes that parents always act with both good will and good
68
sense. Since this may not always be true, the child's wishes should be
respected. In long-term studies, one should reinstate and reevaluate con-
sent from time to time. When an investigator uncovers some potentially •
serious problems during the course of research, the investigator's respon-
sibility is unclear, particularly with regard to confidentiality. The in-
vestigator should allay the fears and anxieties of the subjects after the
study is completed, and provide additional information when necessary. To
assure that scientific objectives do not overshadow an evaluation of the
effects of a study on children, the investigator should be knowledgeable
about their vulnerabilities and capacities, always attending to the social
and psychological child as well as the biological child.
69
. Chapter 6. Psychological Perspective
Lucy Rau Ferguson, Ph.D., a developmental psychologist, wrote a paper
for the Commission on "The Competence and Freedom of Children to Make Choices
Regarding Participation in Biomedical and Behavioral Research." She empha-
sizes, first and foremost, that the child is a person and parental consent
should therefore be a necessary, but not sufficient, condition for children's
participation in research: "Investigators should conduct research so as not
only to respect but to enhance the child's developing capacity for informed
choice." An important aspect of research involving children, she suggests,
is that they can learn from the experience that the generation of knowledge
is, in itself, a good; in addition, the most legitimate motive for involving
children in research is an appeal to their intrinsic curiosity and their
developing sense of altruism.
Investigators should never offer incentives which are so great as to
overcome a child's reluctance to participate, nor should pressure be brought
to bear on peers, parents or others in authority. The child should be
given as much information as he or she is capable of understanding; and this
will vary with the nature of the research, and the maturity of the indivi-
dual child. In general, according to Ferguson, informed consent of the
parents should be sufficient for infants and toddlers; but pre-school and
primary-age children should be given explicit information about what parti-
cipation in research will mean and about the purpose of the research, since
children of this age can understand considerably more than they can articulate.
(It is important to keep in mind "that the investigators should have experience
71
and competence in working with children.) For the pre-adolescent (school-
age) child, participation should be based upon the same principles of in-
formed consent as apply to adult subjects (including, if appropriate,
signing a consent form), although parental consent should be obtained as
well. At this age, children are quite capable of understanding what is
involved in most studies, if the problem is stated in nontechnical lan-
guage. Investigators, according to Ferguson, should never underestimate
the curiosity or the capacity of school -age children for making informed
choices; and participation in research which is an informative and positive
experience can have the function of strengthening a child's scientific curio-
sity. The adolescent should be treated as an adult so far as "nontherapeutic"
research is concerned (although parental consent should be obtained as well
for those who are still legal minors), for it is particularly important to
adolescents that their autonomy and competence be respected.
Ferguson believes that children of all ages should be treated with hon-
esty; therefore, research that involves deception should not be undertaken,
for children will only learn from such experiences that scientists are not
to be trusted. Incomplete disclosure is acceptable, in some instances, so
long as the children are given a fair explanation of what their participation
will involve. Privacy should be protected; and parents of young children
should be informed of any conditions which warrant attention. Parents, and
children who are old enough to understand, should be given reports of the
findings of the research.
72
Chapter 7. Legal Issues
There is currently a legal trend toward enunciation and expansion of
children's rights. Considerable tension remains, however, between emerging
rights of children to exercise self-determination, on the one hand, and the
traditionally-held rights of parents and the state, on the other hand, to
protect children from their own judgment and to insist that their behavior
conform to what is determined to be in their own best interests, in the best
interest of the family unit, or in the best interest of the state.
According to the common law, as in the philosophy of Hobbes, Locke and
Mill, children are chattels of their parents and wards of the state, owing
obedience in return for necessary care. Parents have the authority to con-
trol their children, to educate them, and generally to provide for them, with
the state reserving the right, as poA^M patujie., to intervene when parents
fail in their duty to provide and protect, or when discipline oversteps into
the realm of cruelty. Children have no right to liberty, but only to custody;
and the underlying presumption is that parents and society act in the best in-
terests of the child.^
Children's rights as against their parents or the state have been enun-
ciated recently in several broad areas: education, divorce and custody pro-
ceedings, juvenile delinquency and civil commitment. The notion that parents'
interests always coincide with those of their children, or that the state will
always act in the best interest of its ward, has been challenged and at times
has yielded to a determination that the rights of children may not always be
73
properly represented by their parents or the state. In the area of consent
to biomedical and behavioral research, however, there has been little develop-
ment of a judicial or statutory body of law. Before examining these few artic-
ulated rules, it would be appropriate to review the capacity of children and
the authority of parents to consent to related and other interventions.
The primary issue with respect to the applicability of the doctrine of
informed consent is the capacity of the child to comprehend and weigh the
benefits and risks of proposed research. Although a child may be conclu-
sively presumed to lack the capacity to consent in certain contexts (e.g.,
to contract for non-necessary items or to make a will), there are other situa-
tions in which capacity is an issue of fact to be decided on a case-by-case
basis.
For example, in certain circumstances a child may be precluded from
recovering damages for negligent acts toward the child if the defendant can
prove that the child "assumed the risk." The assumption of risk defense is
a question of fact which depends on finding that the child was aware of, and
appreciated, the known risks in his or her conduct and nevertheless engaged
in it. Thus, in a suit by a 15-year-old high school student against his
school system for severe injury (broken neck) sustained in a football game,
the court stated that an athlete may be taken to consent to physical contact
consistent with the understood rules of the game. On the other hand, chil-
dren at a very young age may be conclusively presumed to be unable to assume
all types of risks.
74
The area of law most pertinent to the issue of consent to research for
the direct benefit of the minor is that involving consent to medical treat-
ment. The issue of consent usually arises in one of three situations. First,
in a suit by a minor against a physician for assault and battery, the physi-
cian will attempt to argue that the minor's consent is a sufficient defense.
Second, a state legislature may create exceptions to the general rule of in-
capacity of minors to consent to medical treatment by permitting consent to
specific treatment without reference to parental consent. Third, a constitu-
tional right of the minor may be violated where the state reinforces parental
authority to consent to certain treatments of a minor without the latter's
consent.
The area of law having relevance to issues of research not involving
direct benefit to the minor concerns consent by a minor-donor to be involved
in skin, kidney or bone marrow transplantation. Finally, there is one re-
ported case specifically dealing with participation of minors in research.
Direct Benefit to the Minor: Law of Treatment . The law in most states
is that parental consent is necessary and sufficient for treatment of persons
under 18 years of age (see Table 1). Three exceptions to this general rule
have been incorporated to various degrees. First, courts have implied legally
valid consent on behalf of the minor when there was an emergency condition
threatening the child's life or serious bodily harm and the parents could not
be reached quickly. Legislatures in a number of states have expanded the
definition of emergency to include immediate danger to the "health" or "mutual
well-being" of a child.
75
Second, courts and legislatures have found "emancipated minors" to be
capable of giving legally valid consent to medical treatment. The definitions
of emancipation have varied somewhat among the states, but usually refer to .■.=
minors who are married or maintain their own residence and manage their fi-
8
nancial affairs. ,_ ■ : '
Third, a minority of courts and legislatures have adopted the so-called
"mature minor" rule. The rule originated in several decisions holding a doc-
tor not liable for assault and battery where the consenting minor patient
(between 17 and 19 years of age) was sufficiently intelligent to comprehend
the nature and consequences of a proposed treatment.^ A few legislatures
have enacted such a rule, thereby making capacity to consent primarily an
issue of fact.'^
Another method for carving out exceptions to the general rule of exclu-
sive parental authority to consent has been legislation of age limitations
on an ad hoc basis. The conditions meriting the attention of the legislature
have involved public health problems with high social costs (e.g., venereal
disease and drug abuse) and other sex-related health care (e.g., contracep-
tion and pregnancy, excluding abortion). Some states have set a minimum age
floor with respect to certain treatments while other statutes permit VD treat-
ment to any consenting minor, (See Table 1.)
While many recent pronouncements of children's rights are articulated
in an affirmative manner, several court decisions have expanded such rights
by striking down statutory restrictions on the autonomy of children. In so
76
doing the courts have limited the authority of parents to act as primary
protector and judge of their children's best interest.
A leading case is Planned Parenthood of Central Missouri v. Danforth J^
where the United States Supreme Court invalidated a state statute requiring
parental consent to an abortion on a minor. Building upon Supreme Court
cases which had found minors to possess protectible constitutional rights,'
the court held, in a sharply divided decision, that the statute, which re-
flected an interest in the safeguarding of the family unit and of parental
authority, impermissibly infringed upon the "competent" 'minor's constitu-
1 o
tional rights of privacy. Vigorous dissents from this opinion supported
the right of parents to guide their children and right of the state to pro-
tect the immature from imprudent decisions.
The Planned Parenthood decision, however, does not provide clear-cut
answers for determining the scope of a minor's right of privacy with respect
to other medical treatments. While the Court emphasized that not every minor,
regardless of age or maturity, could legally consent to an abortion, it did
not set out a test for "competency." Moreover, only an absolute parental
^ veto over the abortion decision was invalidated. In a companion case the
court left open the possibility that requiring parental consultation or a
court order authorizing an abortion if in the minor's best interests may
not "unduly burden" the minor's constitutional right. ^^ Furthermore, the
Court expressly reserved the issue of whether different consent requirements
15
may be maintained for different medical procedures.
77
In Carey v. Population Services International '^ the Supreme Court re-
cently struck down a statute banning the sale of nonprescription contracep-
tives to minors under the age of 16 years, but only four justices relied
on the Planned Parenthood holding on abortion as the a ^ofutlofU rationale
for extending minors' rights to the area of contraceptives. Two justices
joined the result, on the grounds -intM. oLia that the statute prohibited
parents from distributing contraceptives to their children, thereby infringing
their constitutional interests in the rearing of their children. Thus the
issue of the unit of autonomy at stake (and also the standard of judicial re-
view to be utilized in evaluating restrictions on a minor's access to treat-
ments) remains to be decisively settled. Moreover, even the four-man plurality
failed to elaborate upon the statement in Planned Parenthood that not all minors,
"regardless of age or maturity, may give effective consent."'^
With respect to treatment of mental illness, a three- judge federal dis-
trict court has limited parental authority by striking down a statute permit-
ing civil commitment of children to state mental institutions by virtue of
parental consent. The court enunciated various due process rights to which
a minor is entitled, including a hearing, right to counsel and to confront
I witnesses, and requiring the state to prove the need for institutionalization
i
by clear and convincing evidence. (The case was appealed to the Supreme Court,
j which vacated the result and remanded the case for reconsideration by the
I three-judge court, on the grounds that the facts of the case had changed and
required a new review.*-"^) The California Supreme Court has also invalidated
procedures for admitting minors^ if 14 years or older, to state mental hospi-
78
tals upon parental consent where the minor has not voluntarily acquiesced in
the decision and thereby waived his or her due process rights to a commitment
?1
hearing. ■
The state may also limit parental authority in another sphere of medical
treatment decision-making: the decision to refuse medical treatment. The
state may override the parent's refusal to seek treatment by resort to its
pa/LQ,¥U> paVujKi authority, as complemented by "neglect" statutes. When the
child's life is in immediate danger, a court can clearly authorize treatment.
The more difficult cases involve a state claimed need of a minor for elective
surgery that is at odds with the parents' own system of values. Some decisions
superimpose the state's interest in providing a more "normal" psychological
22
environment over the parents' judgment. Other courts, however, have upheld
parental authority to refuse elective surgery, ^-^ especially where the child's
desires have been taken into account.^
In conclusion, a reasonable inference from the law of consent to medical
treatment is that consent to research holding out the prospect of direct bene-
fit is probably similar enough to bring the same doctrines into play. Never-
theless, consent to research has been virtually unanalyzed by courts and legis-
latures. It is possible that age floors for consent to various types of re-
search might be as uneven as age floors for various types of treatment. For
example, state statutes authorizing minors to consent to venereal disease or
drug abuse treatment are silent with respect to consent to behavioral research,
e.g., survey questionnaires regarding minors' need for such treatment. It is
reasonable for a court to construe such legislation as providing for an identical
79
age limit with respect to research on such treatment; answers to such a sur-
vey questionnaire would enable state authorities to design better methods
for effectuating the public health purposes embodied in the statutes. Thus,
a national research policy must be flexible enough to allow for the varying
consent standards among the states for biomedical and behavioral interventions
that hold out the prospect of direct benefit to the child.
No Direct Benefit to the Minor: Law of "Donation ." The only area of
authority in a related context bearing upon the issue of consent to research
interventions that are not for the direct benefit of minor subjects is that
involving donation by minors of kidneys, skin grafts and bone marrow. In
these cases, the donors are undergoing medical procedures that are not for
their direct benefit but rather for the purpose of saving the lives of rela-
tives. Bonner v. Moran ^^ is the leading case on the necessity (but not neces-
sarily the sufficiency) of parental consent for an intervention that involves
risk and no direct benefit to the minor. Bonner was a 15-year-old who was
persuaded by his aunt to donate skin for a graft to his seriously burned
cousin. Bonner's mother did not know of the first operation beforehand. She
was later advised that her son was returning to the hospital to be "fixed up,"
and she did not protest. Subsequently, an action for damages for assault and
battery was brought. Evidence was presented that the mother had publicly ex-
pressed pride in her son's courage. At issue was whether parental consent was
necessary and whether the mother had given consent by implication or ratifi-
cation. The trial court instructed the jurors that if they believed the boy
was capable of understanding the nature and consequences of the operation and
had actually consented, parental permission was not necessary. The jury so
80
found. On appeal, the court held that the jury should have been instructed
that parental consent was necessary, because the operation was not for the
benefit of the child in question and involved "sacrifice on the part of the
infant of fully two months of schooling, in addition to serious physical
pain and possible results affecting his future life."^^ Thus, the trial
court's reliance on a mature minor exception to the requirement for parental
consent was rejected on the ground that such exceptions apply only when the
procedures in question will provide direct benefit to the minor. The issue
of whether concurrent consent on the part of the child was necessary was not
decided.
A series of three Massachusetts cases that approved kidney donations by
teen-age donors to their identical twins focused on the "grave emotional im-
pact" that the healthy twins would suffer if they did not donate to save
their brothers' lives. '^' In all three cases, consent was given by the parents
as well as the minors (one was nineteen years old, two were fourteen years old),
and the court found psychological benefit for the donors. A subsequent Connec-
ticut case involving seven-year-old twins differed in that there was no possi-
bility of consent by a mature minor, although the court found that the young
donor had been informed of the operation and "insofar as she may be capable
of understanding" desired to donate her kidney. ^° Noting that the proposed
operation would be life-saving to the donee, "of some benefit to the donor,"
and of "negligible risk" to both, the court found that it would be inequita-
ble to prohibit parental consent when such consent was favorably reviewed by
a guardian ad tltim and by community representatives including a court of
equity.
81
By contrast, a Louisiana court denied authority to a parent to permit
a 17-year-old mentally retarded boy to donate a kidney to his 33-year-old
30
sister. There, the court reasoned that the closest analogy in Louisiana
law was that of donation of a minor's property, and that:
Since our law affords this unqualified protection against
intrusion into a comparatively mere property right, it is
inconceivable that it affords less protection to a minor's
right to be free in his person from bodily intrusion to the
extent of loss of an organ unless such loss be in the best
interest of the minor.
The court found benefit to the donor to be "not only highly speculative
but . . . highly unlikely," and concluded that the operation would be against
his best interest.
In a case more relevant to the research context, where the proposed pro-
cedure involved donation of bone marrow rather than permanent loss of an or-
gan, a Massachusetts court observed that the evidence did not permit a find-
op
ing that the procedure would be of any benefit to the six-year-old donor. '^'^
The court permitted the operation nonetheless, saying it did "not believe
that a finding of benefit to the donor is essential, or that the absence of
such a finding is fatal, to the allowance of such a transplant," and noting
that risks to the donor were "minimal." The court found that the parents
had authority to consent for the operation, but that their consent should be
subject to court review because of the possibility of conflict between their
responsibility for the care and custody of the donor, and their similar re-
sponsibility for the donee.
82
Mem' ken v. Cressman ^-^ is virtually the only relevant case involving
consent for the participation of children in research (other than the bone
marrow cases). In Merriken , a suit brought by a junior high school stu-
dent and his mother, a federal district court enjoined implementation of an
experimental drug abuse prevention program. The program required students'
responses to questionnaires that asked highly sensitive questions concerning
their home life, an area protected by Supreme Court decisions, and also
asked students to identify classmates whose behavior was unusual or inappro-
priate. On the basis of such information, compulsory remediation was to be
instituted by teachers who lacked proper training in psychological therapy.
Further, the results of the questionnaires were to be made available to in-
dividuals not involved in the program, such as athletic coaches, administra-
tors, and members of the. PTA and school board. When the suit was filed, the
defendants had planned what the court called a "book-of-the-month-club" ap-
proach to obtaining parental consent, in which silence would be construed as
acquiescence. (They later offered to change that approach and require writ-
*
ten parental consent, and also to give students notice that they were free
to return a blank questionnaire.)
The court found that the program infringed on the child's constitutional
right of privacy, and further that "there probably is no more private a rela-
tionship, excepting marriage, which the Constitution safeguards than that be-
tween parent and child." " Finding defects in the procedures for parental con-
sent, which precluded knowledgeable waiver of their children's rights, the
court raised but did not resolve the issue of a requirement for consent of the
83
children. It did conclude, however, that the program would be administered
"without the knowing, intelligent, voluntary and aware consent of parents
or students. "-^^
This case, then, supports the necessity (but not necessarily the suffi-
ciency) of parental consent for participation of children in research, just
as Bonner did with respect to medical interventions for the benefit of others.
Whether courts would require the assent of children, in addition, remains un-
clear.
84
TABLE i
CONDITIONS DEFINING ABILITY TO CONSENT TO MEDICAL CARE (BY STATE STATUTE)
Chart prepared by Commission staff in June 1976 (revised June 1977)
(Source: Hospital Law Manual)
General Conditions Defininc
Ability to Consent
Specific Treatments Which May be Obtained by
Minors without Parental Consent
Age
C
)verridtng Circumstances
STATE
Married or
ennancipated
Pregnant
or parent
Other
V.D.
Addiction
Preg-
nancy
Contra-
ception
Other
Ala.
14
X
X
high school graduate
X
X
X
emergency or any
reportable disease
Alaska
19
X
X
X
X
Ariz.
18
X
X
12
rape victim (over 12 yrs.)
Ark.
18
X*
"of sufficient
intelligence"
X
X^
Cal.
18
X
in armed services
12
X
X
reportable communicable
disease (over 12 yrs.)
Colo.
18
X*
X
X
por
parent
Conn.
18
X
X
Dela.
18
X
12
12^
communicable disease
(over 12 yrs.)
DC.
18
X
X
X
X
psychological
disturbance
Fla.
18
X
X
X^
por
parent
blood donation (over
1 7 yrs.) or emergency
Ga.
18
X
x'
X
X
X
Hawaii
18
14
14
Idaho
18
14
16
infectious or communi-
cable disease (over 14 yrs.)
III.
18
X
X
12
X
m, p or
parent
emergency or referred for
treatment by physician,
clergy, or planned
parenthood agency
Ir<d.
18
X
x
X
Iowa
18
X
16
X may consent at any age under such
circumstances or for such treatment
a except abortion
m married
p pregnant
• unmarried, emancipated minors
must be over 15 yrs.
85
CONDITIONS DEFINING ABILITY TO CONSENT TO MEDICAL CARE (BY STATE STATUTE)
General Conditions Defining Ability to Consent
Specific Treatments Which May Be Obtained by
Minors without Parental Consent
Age
Overriding Circumstances
STATE
Married or
emancipated
Pregnant
or parent
Other
V.D.
Addiction
Preg-
nancy
Contra-
ception
Other
Kan.
18
no parent or guardian
available (over 16 yrs.)
X
X
X**
Ky.
18
X
X
X
X
X
La.
18
X
X
actual or believed illness
Including but not limited
to V.D. and drug addiction
Me.
18
X
X
Md.
18
X
X
X
X
X
X
emotional disorders
(over 16 yrs.)
Mass.
18
X
X
X
12
X
emergency or disease
"dangerous to the
public health"
Mich.
18
X
in armed
services
X
X
kidney donation to
parent, sibling, or
child w/court approval
(over 14 yrs.)
Minn.
18
X
X
X
X
X
blood donation
(over 17 yrs.)
Miss.
21
X
"of sufficient
intelligence"
X
X
Mo.
21
X
X
X^
Mont.
18
X
X
high school graduate
X
X
X
X
acute psychological
disturbance and no parent
or guardian available
Neb.
19
X
X
Nev.
18
X
X
X
N.H.
18
14
12
N.J.
18
X
X
X
N.M.
18
X
X
X
X may consent at any age under such
circumstances or for such treatment
a except abortion
m married
p pregnant
** no parent or guardian available
86
cc
NDI
TIONSDEF
General C
IIMING ABILITY TO CONSE
onditions Defining Ability to Consent
NT TO MEDICAL CARE (BY STATE STATUTE)
Specific Treatments Which May Be Obtained by
Minors without Parental Consent
Age
Overriding Circumstances |
STATE
Married or
emancipated
Pregnant
or parent
Other
V.D.
Addiction
Preg-
nancy
Contra-
ception
Other
N.Y.
18
X
X
X
X
N.C.
18
X
X
N.D,
18
14
14
Ohio
18
X
X
Okla.
18
X^
x"
in armed services
X
X^
Ore.
15
X
12
X
X
Pa.
18
X
X
high school graduate or
professing competency
X
X
any reportable disease
or emergency
R.I.
18
X
emergency (over 16 or m)
S.C.
16°
X
X
"necessary services"
S.D.
18
X
Tenn.
18
X
m, p,
parent, or
referred
Texas
18
X
in armed services
^
13
X^
any reportable
communicable disease
Utah
18
X
X
Vt.
18
12
12
Va.
18
X
X
X
X
Wash.
18
X=
14
W.Va.
18
X
X
Wise.
18
X
Wyo.
19
X
X may consent at any age under such
circumstances or for such treatment
87
a except abortion
m married
p pregnant
o except operations
s spouse must be of legal age
FOOTNOTES
1. Kleinfeld, The Balance of Power Among Infants, Their Parents and the
State, Parts II and III, 4 Fam. L.Q . 409 (1970), and 5 Fam. L.Q . 63
(1971); see also Rodham, Children Under the Law, 43 Harvard Educa -
tional Review 487 (1973).
2. See generally Xd. _ '
3. See Vendrell v. School District , 233 Ore. 1, 376 P. 2d 406 (1962).
4. E.g., Greene v. Watts , 210 Cal . App. 2d 103, 26 Cal . Rptr. 334
(1962) (3 1/2 year old).
5. Some states set a lower standard, e.g., Alabama (14 years); South
Carolina (16 years).
6. W. Prosser, Torts 103 (4th ed. 1971).
7. Ga. Code Ann. § 88-2905 (1971).
8. See, e.g., Colo. Rev. Statute § 13-22-103 (1973).
9. Younts v. St. Francis Hospital , 205 Kan. 292, 459 P. 2d 330 (1970) (17
year old consent to skin transplant for damaged finger); Lacey v. Laird ,
166 Ohio 12, 139 N.E.2d 25 (1956) (18 year old consent to plastic sur-
gery on nose); Bakker v. Welsh , 144 Mich. 632, 108 N.W. 94 (1906) (17
year old consent to surgery to remove tumor).
10. E.g., Miss. Code Ann. § 41-41-3(h) (1972); see N.H. Rev. Stat. Ann.
§ 318-B, 12-a (Supp. 1975).
11. 428 U.S. 52 (1976).
12. Goss V. Lopez , 419 U.S. 565 (1975) (procedural due process in context
of school discipline); Tinker v. Pes Moines School District , 393 U.S.
503 (1969) (freedom of expression in school); In re Gault , 387 U.S. 1
(1967) (right to counsel at delinquency proceeding).
13. 428 U.S. at 72-75. .
14. Bellotti V. Baird , 428 U.S. 132, 147-50 (1976).
15. Id. at 857; see Cal. Welf. & Inst'ns. Code § 5325 eX Atq. (prohibition
of psychosurgery on persons under 18 years of age); Aden v. Younger , 57
Cal. App. 3d 662, 129 Cal. Rptr. 535 (1976) (constitutional issues raised
in regulation of experimental psychosurgery; prohibition on minors not
directly considered).
16. 52 L. Ed. 2d 675 (1977).
17. Id. at 689-94 (Brennan, J.) (plurality opinion).
18. Id. at 699 (Powell, J., concurring); Id. at 702-03 (Stevens, J., con-
curring) .
19. Id. at 690 n.l6 (Brennan, J.) (plurality opinion).
20. Bartley v. Kremens , 402 F. Supp. 1039 (E.D. Pa. 1975), vacated and
remanded , 45 U.S.L.W. 4451 (1977).
21. 19 Cal. 3d 655 (Crim. No. 19558, July 18, 1977).
22. E.g., Matter of Sampson , 65 Misc. 2d 658, 317 N.Y.S.2d 641 (1970),
aff d , 37 App. Div. 2d 668, 323 N.Y.S.2d 253 (1971), aff d per
curiam , 29 N.Y.2d 900, 328 N.Y.S.2d 686 (1972) (state imposed cos-
metic surgery on face of 15- year-old boy).
23. In re Hudson , 13 Wash. 2d 673, 126 P. 2d 765 (1942) (parental refusal
to permit amputation of deformed arm of 11 -year-old daughter upheld).
24. Matter of Seiferth , 309 N.Y. 80, 127 N.E.2d 820 (1955) (parental refusal
to permit corrective surgery of 14-year-old boy's harelip and cleft
palate upheld where minor in accord with parents' desires).
25. 126 F.2d 212 (D.C. Cir. 1941). -
26. Id. at 123.
27. Masden v. Harrison , No. 68651 Eq. (Mass. Super. Ct., June 12, 1957);
Huskey v. Harrison , No. 68666 Eq. (Mass. Super. Ct., August 20, 1957);
Foster v. Harrison , No. 68674 Eq. (Mass. Super. Ct., November 20, 1957);
discussed in Louisell and Williams, Medical Malpractice II 19.14 (1976).
28. Hart v. Brown , 29 Conn. Supp. 368, 289 A. 2d 386 (1972).
29. Id. at 391.
30. In re Richardson , 284 So. 2d 185 (La. App. 1973).
31. Id. at 187.
32. Nathan v. Farinelli , Civ. No. 74-87 (Mass. Super. Ct., July 13, 1974).
33. 364 F. Supp. 913 (E.D. Pa. 1973).
34. Nielsen v. The Regents of the University of California , No. 665-049
(Cal. Super. Ct., County of San Francisco, filed Sept. 11, 1973).
89
35. See Pierce v. Society of Sisters , 268 U.S. 510 (1925); Meyer v .
Nebraska , 262 U.S. 390 (1923).
36. 364 F. Supp. at 918.
37. Id. at 922.
90
Chapter 8, Ethical Issues
The general purpose of research involving children is to obtain scien-
tific information about them. Often the research provides some direct bene-
fit to the subjects involved in the research. However, some research may
produce benefits only for other children, and frequently it is quite un-
certain whether the subjects themselves will ultimately benefit from the
research. In some cases benefits are long-range or unpredictable, and the
major objective is to develop a body of knowledge. Ethical issues about
the involvement of children arise because of competing answers to the fol-
lowing question: Under what conditions (if any) are these various types
of research justified? When the objective of procedures is that of directly
benefiting the subjects, the research is generally agreed to be justifia-
ble, under certain limiting conditions, if there is a reasonable prospect
that the subjects will benefit. However, research in which procedures pre-
sent no prospect of direct benefit to the subjects raises a variety of ethi-
cal problems about the protection and the rights of children and about the
authority of parents. Although only alluded to in classical ethical codes
and regulations, these problems have received extensive attention in recent
ethical literature. . :
Codes and Regulations . The Nuremberg Code (1949) has seemed to some to
preclude the participation of children in research. The first principle of
that code states explicitly:
The voluntary consent of the human subject is absolutely
essential. This means that the person involved should
have the legal capacity to give consent, . . .-\
91
The apparent clarity of this statement, however, is clouded by the written
statements of two individuals who participated in the drafting of the Code.
Leo Alexander, whose first draft of principles formed the basis of the Code,
has written that the original draft contained provisions for consent by next
of kin on behalf of incompetent patients, but that the judges omitted those
provisions in the final version "probably because they did not apply in the
specific cases under trial. "^ Similarly, Andrew Ivy, chief medical consul-
tant to the War Crimes Trials, wrote (in the same year the Code was pub-
lished) that: I
The ethical principles involved in the use of the mentally
incompetent are the same as for mentally competent persons.
The only difference involves the matter of consent. Since
mental cases are likened to children in an ethical and legal
sense, the consent of the guardian is required. 3
The record does not show whether the judges at Nuremberg disagreed with their
medical consultants on this matter or whether, as Alexander suggests, they
simply followed judicial custom by limiting their opinion to the facts of
the case at bar.
The Medical Research Council of Great Britain took the position in 1963
that young children should not be subjects of "nontherapeutic" research if
that research "may carry some risk of harm."^ Their general rule is that if
a child is under 12 years of age:
information requiring the performance of any procedure
involving his body would need to be obtained incidentally
to and without altering the nature of a procedure intended
for his individual benefit. 5
92
If the child is over age 12, his or her consent should be obtained, and its
validity would depend upon a showing that the child understood the implica-
tions of the procedures involved.
The Declaration of Helsinki ," published by the World Medical Associa-
tion in 1964, provides, with respect to "nontherapeutic" research, that "if
[the subject] is legally incompetent the consent of the legal guardian should
be secured."* The acceptance of this code by the American Society for Clini-
cal Investigation, the American College of Physicians, the American College
of Surgeons, and particularly the American Medical Association resulted in
the general acceptance throughout this country of third-party permission for
research employing interventions that are not for an incompetent subject's
direct benefit.
The 1971 Institutional Guide to PHEW Policy for the Protection of
Human Subjects required the consent of a subject "or his authorized repre-
sentative." It did not define "authorized representative," but cautioned
that:
The review committee should consider the validity of
consent by next of kin, legal guardians, or by other
qualified third parties representative of the subjects'
Interests. In such instances, careful consideration
should be given by the committee not only to whether
these third parties can be presumed to have the neces-
sary depth of interest and concern with the subjects'
rights and welfare, but also to whether these third
parties will be legally authorized to expose the sub-
jects to the risks involved. o
* The 1975 revision states, as a basic ethical principle, that: "When the
subject is a minor, permission from the responsible relative replaces that
of the subject in accordance with national legislation."
93
DHEW invited comments in 1973 on the proposal that parental or guardian
consent be supplemented both by the judgment of a consent committee and by
requirements for the assent of the child or incompetent.^ The following
approach was taken regarding the refusal and consent of children:
Although children might not have the capacity to consent
on their own to participate in research activities, they ^
must be given the opportunity (so far as they are able)
to refuse to participate. The traditional requirement
of parental consent for medical procedures is intended
to be protective rather than coercive. Thus, while it
was held to be unlawful to proceed merely with the con-
sent of the child, but without consent of the parent or
legal guardian, the reverse should also hold.-jQ
This proposal to require assent of the child was adopted for intramural
research by the NIH Clinical Center on July 14, 1975.'^
Current DHEW regulations provide that consent may be obtained from an
individual's "legally authorized representative," which is defined as "an
individual or judicial or other body authorized under applicable law to con-
sent on behalf of a prospective subject to such subject's participation in
the particular activity or procedure.""^ Strictly construed, this provision
would permit third-party permission only in those jurisdictions which speci-
fically authorize a third party to consent for another's participation in re-
search. While parental authority to consent for medical care is clear, there
is no statute or judicial decision granting such authority for nonbeneficial
procedures. (See the discussion in Chapter 7 of this report.)
Ethical Positions in Recent Literature . At least five different posi-
tions on the involvement of children in research can be found in recent litera-
ture.
94
(1) The most restrictive position is found in the writings of Paul
Ramsey. He argues that research which does not directly benefit indivi-
dual children is always ethically impermissible. His argument rests on
the general viewpoint that "nontherapeutic" research should never be per-
formed without the informed consent of the subject. Since young children
are not capable of giving informed consent, it is a short step to the conclu-
sion that no research ought to be performed on them unless the research holds
out the possibility of direct benefit. In his book, The Patient as Person ,
Ramsey argues as follows:
A parent's decisive concern is for the care and protection
of the child, to whom he owes the highest fiduciary loyalty,
even when he also appreciates the benefits to come to others
from the investigation and might submit his own person to
experiment in order to obtain them.
This is simply the minimum claim of childhood upon the
adult community, whose members may make themselves joint ad-
venturers or partners in the enterprise of medical advance-
ment at cost to themselves if they win.-jo
Ramsey distinguishes "beneficial research," for which parental consent is a
proper fulfillment of the fiduciary duty, from "nonbeneficial research," for
which he considers third-party permission a breach of the fiduciary duty.
It is not merely the exposure to possible risk that he finds unacceptable.
Rather, it is the abrogation of "the right of each of us to determine for
ourselves, not alone the extent to which we will share ourselves with others,
but the timing and the nature of any such sharing. "^^ It is thus a claimed
violation of respect for persons (by treating others as a means to one's
own end) which is morally unacceptable to Ramsey: "where there is no possi-
ble relation to the child's recovery, a child is not to be made a mere object
95
in medical experimentation."^^ Still, Ramsey is concerned with the risk of
harm as well as with the violation of aytonomy. He argues that the impera-
tive to avoid evil has a moral primacy in biomedical research over the im-
perative to do good, and he takes this priority as one more support for his
general position.'^ Nonetheless, it is the alleged use of human beings
merely as means to others' ends that most deeply informs Ramsey's polemic
against "nontherapeutic" research.
Ramsey proposes to give ethical primacy to the protection of noncon-
senting subjects against wrongful treatment. While this general position
must be commended, Ramsey's views are subject to a number of objections.
First, it is important to distinguish those who refuse to consent to parti-
cipation in research from those who are not fully qualified to consent to
participatior,. It would be generally conceded that children who refuse to
agree to participate in "nonbeneficial " research should not be involved.
But it appears to be increasingly the case that most children are willingly
involved in research and give their assent (when capable). Second, Ramsey
neglects discussion of the low level of risk involved in most research in-
volving children. His conclusions (though not his actual arguments) would
be more supportable if there were a widespread risk of serious harm. In
fact, however, much biomedical and behavioral research involves no more risk
to children than those risks encountered in their daily lives. Ramsey's
proposals for curbing research in general, if acted upon, would render im-
permissible research that is only observational, or merely uses questions,
or involves only paper and pencil tests or procedures of a routine medical
96
examination. While everyone would agree that the line specifying permissi-
ble risk must be drawn somewhere, Ramsey's absolute prohibition seems too
restrictive. Ramsey's argument is internally consistent on these matters,
in that he would prohibit all research without regard to risk or to the
assent of children. It is his treatment of these relevant factors (risk
and assent) as irrelevant which is unacceptable J'
Third, Ramsey's position rests on a false dichotomy between research
intended to benefit subjects directly -- which he concedes is permissible --
and research intended to develop more knowledge. Much research does not fit
neatly into either category, since the outcome is uncertain and the research
may or may not benefit the subjects involved. Research on chronic diseases,
for example, may or may not directly benefit those involved in the research,
contingent upon the results of the research. Indeed, the possibility of
(even remote) future benefits for the subjects can seldom be ruled out from
the beginning.^° ^ , ' ■ , ,
This problem introduces a further problem about the meaning and scope
of the term "research," as Ramsey employs it. Research, by definition, is
intended to develop general knowledge. Therapy, by definition, is for the
benefit of an individual and therefore does not inherently involve any
general izable component. The term "therapeutic research" thus mixes together
two quite different ingredients, and it remains unclear what "therapeutic
research" could mean. There are dangers in this unclarity. On the one
hand, there is the danger that simply because a benefit (therapy) is included
in a "therapeutic" research protocol, all sorts of additional interventions
97
not germane to the therapeutic intervention but useful for general know-
ledge can be regarded as justified (under Ramsey's scheme). On the other
hand, if a quite narrow but nonetheless reasonable interpretation of "re-
search" is accepted, then one literally could never do any "research" at
all, because the research itself (e.g., data analysis) is not therapeutic.
Ramsey can perhaps introduce further distinctions to handle some of these
problems -- for example by arguing that "therapeutic research" is a certain
kind of mixture of controlled studies of alternative therapies, when all
treatments are thought to be equally efficacious. But as his work now
stands there remain conceptual unclarities which introduce needless con-
fusion.
Ramsey at one point acknowledges that even if there were powerful
moral reasons for doing "nontherapeutic research with uncomprehending sub-
jects" such as children, "it is better to leave [this] research imperative
in incorrigible conflict with the principle that protects the individual
human person from being used for research purposes without either his ex-
pressed or correctly construed consent. ^ Ramsey argues that it would be
"immoral" either to do or not to do the research, but he maintains that one
should "sin bravely" in the face of this dilemma by sinning on the side of
avoiding harm rather than attempting to promote welfare. But why must a
calculation of benefits and harms always fall on the side of preventing
research? In those cases where potentially great therapeutic benefits may
well result from research and only minimal risk is involved, it may be
reasonably argued that the calculus of morally right actions has shifted.
98
Ramsey attempts to support his view by appeal to the Kantian maxim that
persons ought to be treated as ends only, and never merely as means. But
what is it, in the context of research, to be treated merely as a means?
When a soldier is conscripted, he is treated as a means (even against his
will, in some cases). But he is not treated merely as a means, for none
in the military hierarchy is free to do anything with a soldier he wishes.
Similarly, a child involved in research may be used as a means, but not
merely as a means; for no investigator is free to use a child in any way
he wishes. The question remains whether the child is being used in such
a way that the treatment qualifies as immoral treatment. And if the child
is exposed only to minimal risk (with judicious parental permission and
the child's agreement), while substantial benefit may accrue to others, it
is far from obvious that any immoral treatment is present. If there were
some reason for supposing that children would regard themselves as being
violated or as being used as mere means, Ramsey's argument would be
strengthened-, but in a world where many adults feel themselves morally
obliged to help those in need, there is no reason to attribute an unduly
selfish attitude to children, as Ramsey's argument often seems to presup-
pose. Moreover, as Benjamin Freedman has argued, even if children occupy
a dependent, morally different status from that of adults -- as Ramsey con-
tends -- it does not follow that parents are derelict in their duty in con-
senting for children to participation in research. Even though children
have some claims upon us for protection, participation in research does not
seem to violate their rights unless such participation constitutes a harm-
ful invasion.^"
99
(2) The fact that some research on children involves minimal risk and
holds out the prospect of benefit for the class of children (but presumably
not direct benefit to the research subjects themselves) has been the deci-
sive factor in motivating some writers to accept less stringent criteria
than Ramsey's. One example is Richard McCormick, who has written in opposi-
tion to Ramsey from the perspective that children have obligations to parti-
cipate in research. McCormick employs a natural law foundation for his ar-
guments. He maintains that a child ought to do something if that action is
expressive of basic values of human nature or purposes of human life. In
the case of therapy, for example, it is a reasonable presumption that the
child would consent because (in light of the normative ideal of health) the
child ought to promote his own health. Similarly in the "nontherapeutic"
case, according to McCormick, it is a reasonable presumption that the child
would consent because (in light of the normative ideal of contributing to
the health of others) the child ought to choose to participate in research.
There is a general moral obligation to help others when there is little
cost to oneself. Because children (like all individuals in society) ought
to benefit others by their actions and would so act if they had a proper
moral perspective, it is legitimate to involve them in research (provided
it is of no more than minimal risk). McCormick's presumption is not that
someone would actually act in a certain way but only that another may validly
presume consent because the act is right. Parental consent is said to be
morally valid for both "therapeutic" and "nontherapeutic" contexts, because
it is based on a reasonable presumption of the child's obligations:
100
. . . there are things we ought to do for others simply
because we are members of the human community. ... If
it can be argued that it is good for all of us to share
in these experiments, and hence that we ought to do so
(social justice), then a presumption of consent where
children are involved is reasonable and proxy consent
becomes legitimate. 21
In sum: the parent is the vehicle for choosing what the child should
rightly choose if he were so situated that he knew what he ought to do.
McCormick's position is subject to a variety of objections. There are
at least two possible problems with his claim that we can presume consent
because a child ought to consent. First, natural law arguments have been
subjected to sharp criticism in ethical theory. In particular, one common
objection to natural law theory is that it does not follow from the wide
or even universal sharing by human beings of certain values or purposes
(e.g., health, happiness, etc.) that human beings ought to promote those
values or purposes. For example, from the value human beings place on
propagation of the species it does not follow that all persons ought to
propagate at will or even that they should propagate at all. It does not
follow even if such a value is basic to human nature. This apparent defi-
ciency in McCormick's position is important, since if his natural law
foundation is unsupportable, the entire position on children is groundless.
A second possible problem with McCormick's position resides in the
claim that consent may validly be presumed where there is an underlying
obligation. There are probably numerous activities in which adults ought
to participate, but to which many would not consent. The whole point of
101
obtaining a person's consent is to protect his autonomy. What one person
will consent to may vary significantly from what another will consent to
because of basic differences of value. To respect persons is to respect
their right to their own evaluative choices, including their right not to
perform certain actions which other persons believe, with some justifi-
cation, that they ought to perform. While we have a moral right to demand
that individuals fulfill their obligations, some obligations are created
only by an individual's own commitments, and we often have no right to
demand the commitment itself. Consent is such a commitment, and absent
the commitment no valid consent can be presumed (this much is true in
Ramsey's position). .
Accordingly, it seems certain that we could never validly presume con-
sent on the part of a competent adult subject merely because the person
ought to consent. How, then, can consent of the child be validly presumed?
As Ramsey has argued, McCormick's position "amounts to the destruction of
the protections consent-language was designed to afford. "^^ Consent can
rarely be presumed, and there seems no way it can be presumed on the part
of a child. In short, perhaps the gravest deficiency in McCormick's posi-
tion is its very core: the notion that the child's consent can be validly
presumed.
Ramsey has generalized this conclusion in the following way: if
McCormick's standard is used,
. . . then anyone -- and not only children -- may legiti-
mately be entered into human experimentation without his
will or unwillingly. ... If a child may be treated as
102
an adult who would will what he should, then any
other nonvolunteer may be treated simply as a child
^ who . . . would will what he should . Any nonvolun-
teer may be treated as a child who does not will as
he ought. 23
Ramsey's point is that 1f consent can validly be presumed because of what
persons ought to do, then (1) it is hard to find a principled basis for the
claim that there is any morally relevant difference between adults and
children, and (2) it would follow that the general conscription of adults
is permissible. Ramsey's argument does not constitute an objection to
McCormick, from one perspective, since McCormick actually favors the con-
scription of adults. The pertinent point, however, is about consent, not
about conscription. The form of McCormick's argument is: if one ought to
do it, then consent may be validly assumed. But consent is precisely what
may not be assumed even if one ought to do it. One reason why the require-
ment of informed consent has become so important in recent years is that
the consent of some subjects was never solicited, because a prior judgment
had been made that they ought to participate.
Moreover, it is not even clear, based on McCormick's arguments, that con-
sent should be a relevant consideration. If a child ought to do something and
the obligation justifies the child's doing that thing, then the consent of
his parents could neither validate nor invalidate his participation. Parental
consent is simply irrelevant to the justification for involving the child in
research. To put this point another way, McCormick operates with two levels
for the justification of involving children: natural law and consent by
103
third parties. If the natural law justification is correct, it actually
undermines the consent model by rendering it gratuitous.
A possible response by McCormick to some of these arguments is con-
sidered at the end of the next section (3). But it is worth mentioning at
this point that an alternative interpretation of McCormick 's arguments to
the one presented above might be offered. In his later writings McCormick's
major conclusions appear anchored in the argument that all members of
society, including children, have minimal obligations to benefit other mem-
bers of society. These obligations are created by social circumstances
(rather than by some general property of human nature). Among these obli-
gations is that of participating in minimal risk biomedical or behavioral
research. Because of these social obligations the child should be willing
to participate in research; and parents may be empowered to consent for the
child's participation whenever the child should be willing to be involved
in the research if the child could comprehend and consent. On this alter-
native interpretation, "proxy consent" is merely a device to protect the
child, and plays no more substantive role in the argument. That is, the
obligations children have justify using them, and consent is merely a pro-
tective device that plays no role in the justification. McCormick's posi-
tion is thus turned into a "presumed duty" rather than a "presumed consent"
position. If this alternative reading of McCormick is preferable, then his
position is perhaps closer to the one that is presented in section (5),
below.
104
(3) A variant of McCormick's stance might be developed along lines
proposed by Stephen Toulmin^^ in the course of considering the justifica-
tion of fetal research. He suggests that ii/stead of beginning with what
children ought to do, we might ask whether it may be presumed that they
could not reasonably object if they were capable of understanding what is
at stake and of making a decision in their own right. This strategy is
thought by Toulmin to free the theory of the objection of imputing obli-
gations to children and to reconcile McCormick's approach with common public
policy judgments about the validity of involving children in research.
Toulmin's proposal is distinguishable from the two positions previously
outlined by its philosophical basis. Rather than using a theory of informed
consent or natural law, Toulmin makes an appeal to what the reasonable per-
son would agree to choose -- or, as he states it negatively -- what the
child could not reasonably object to.
A roughly parallel view, but with an emphasis on the problem of consent,
has been advanced by Victor Worsfold.^^ As is common, he distinguishes be-
tween those children who have attained the age of reason and those who have
not. For those who have not -- the class discussed by Toulmin -- Worsfold
suggests that the absence of the ability to make judgments justifies deci-
sions by others (parents), although these must "be guided by the individual's
own settled preferences and interests insofar as they are not irrational, or
failing one's knowledge of these, by [some] theory of primary goods. "^" In
judging the right course, he says, "We must be able to argue that with the
development or the recovery of his rational powers the individual in question
105
will accept our decision on his behalf and agree with us that we did the best
thing for him."^'' This position is the positive side of the one proposed by
Toulmin. Rather than holding that the child could not reasonably object,
Worsfold's criterion is that the reasonable child would approve, in retro-,
spect, an invitation to be involved in research. Additionally, Worsfold
holds that children of sufficient understanding have the right to make
their own decisions; and he proposes that younger children who are incapa-
ble of making judgments entirely on their own nevertheless should be lis-
tened to and their preferences taken into account by those who decide on
their behalf. .
Several possible responses to these theories may be mentioned. In
a paper written for the Commission on "Rights, Duties, and Experimenta-
tion on Children: A Critical Response to Worsfold and Bartholome," Stanley
Hauerwas challenges the current preoccupation with the notion of children's
rights. The language of "rights," Hauerwas suggests, is not entirely appro-
priate to, and in fact is misleading for, an ethical analysis of the place
of children as research subjects, although such language may facilitate a
formulation of appropriate policy. He argues that "rights language," as
applied to the family, inclines us to conceptualize the family as a con-
tractual society of individuals -- which he believes it is not. As a sub-
stitute, Hauerwas proposes that the idea of parental duties and responsi-
bilities toward their children {I.e.., to love, protect and educate them)
provides a better ethical framework on which to base such policy. He focuses
on the historical view that being a parent involves an obligation to care for
106
and to educate one's child in a manner appropriate to making the child a
full participant in the community. His central argument is that the child
ought to be conceptualized as a family member, and because of this special
position the consent and guidance of parents is relevant to the participa-
tion of children. For Hauerwas, accordingly, making a case for children's
"rights" as Worsfold does runs the risk of destroying what being a child
means, by ignoring that a child's need is not for "rights," but rather
for trust, love and care.
Whatever the merits of Hauerwas' arguments, perhaps the major problem
with the reasonable consent theory resides in the flexible and ambiguous
term "reasonable." The reasonableness of nonparticipation in an activity
that is primarily charitable or for the benefit of others can be judged
only by reference to a person's reasons for nonparticipation. In the case
of children, possible reasons for nonparticipation must be projected by
others, and a decision about the reasonableness of these reasons must be
made by others. This judgment does not centrally involve inferring what
a child would do if he could consent. It is a judgment of reasonableness
based on a standard that is not the child's, and hence is external to the
standard of what the child would do if he could choose. But what precisely
is that standard? Is it reasonableness in light of the importance of the
knowledge to be gained? Reasonableness in light of the values of the re-
search community? Reasonableness in the eyes of the parents?
Even more problematic is the very justification of the use of children
by appeal to reasonableness. Many things might be done to nonconsenting
107
subjects which they cannot reasonably (in the eyes of most) object to, and
yet we would not permit such actions to be performed. The mere lack of a
reasonable objection does not justify appropriating others. It seems,
moreover, that the reasonable consent position encounters some of the same
problems as McCormick's position because it is too broad in scope. If
lack of a reasonable objection or reasonable presumption of a later agree-
ment justifies appropriation, then it justifies drafting adults as well as
children. . ■ ■ • '
Presumably Toulmin, McCormick and others would argue that the morally
relevant difference between a competent adult and a child is that the adult
can informedly consent and the child cannot. But why should refusals to
consent by adults override drafting them if their refusal is not "natural"
or reasonable? The answer must be that we would be exhibiting a lack of
respect for them by violating their autonomy and that this disrespect is
not being exhibited toward the child, because he cannot express autonomy.
While this reply is no doubt correct, it fails to exhibit why mere absence
of a reasonable objection justifies any use of another person. Or, to put
the point another way, it may be that the absence of a reasonable objection
by another person is a necessary condition of using the other person for re-
search, but it is not sufficient. And if it is an insufficient reason,
then the reasonable consent position only tells us one condition that must
be satisfied if we are to do research on children. It does not tell us
that we may do the research if there is an absence of a reasonable objec-
tion; yet this conclusion is what is primarily desired in a principled
justification.
108
(4) Some writers have attempted to mediate between Ramsey's entire
exclusion of the class of children and McCormick's (and others') apparent
entire inclusion of the class. These writers have suggested that children
old enough to be educated can be aided in their education by participation
in research, but not at earlier ages. The justification for participation,
then, is moral development; and if there can be no moral development through
participation, the justification is lost. Perhaps the first to suggest this
approach was Henry Beecher. In Research and the Individual he suggested,
without further elaboration, that
Parents have the obligation to inculcate into their
children attitudes of unselfish service. One could
■ hope that this might be extended to include partici-
pation in research for the public welfare, when it is
important and there is no discernible risk.po
This kind of position has been defended in a paper written for the Com-
mission by William Bartholome.'^" He discusses the involvement of children
from age five to seven through age 14 to 16 in research activities. He
criticizes Ramsey's total exclusion of children from "nontherapeutic" re-
search as harsh, and suggests that to focus exclusively on informed consent
(as Ramsey does) as the moral basis for including subjects in research is to
prejudge the answer to the question whether children may participate in "non-
therapeutic" research. At the same time Bartholome agrees with Ramsey that
interventions in the lives of children can be justified only if they are to
benefit the child. These two authors largely differ over what shall count
as a benefit. While Ramsey considers only therapy to be beneficial, Beecher
and Bartholome consider improved moral character to be a benefit.
109
Bartholome criticizes McCormick for presuming that adults are able to
know what a child should want and rejects McCormick's suggestion that there
are certain things a child "ought to do." Children are not morally "trans-
parent," he argues, and thus no adult can know what a particular child
should choose. And since it cannot be asked what they would choose, only
their needs should be considered in asking about their participation in
research. Even if there are certain things that a child ought to want to
do for others, Bartholome claims, no one has the right to determine how,
when and in what manner such obligations should be fulfilled. Bartholome
also disputes what he takes to be McCormick's argument that we owe to
future generations the cure or prevention of certain diseases and that,
in general, involvement in "nontherapeutic" research is obligatory for
everyone. Bartholome prefers to see such rewards for future generations
as "gifts" rather than as obligations required by justice or by social
need.
To resolve the conflict between the two polar positions exemplified
by the writings of Ramsey and McCormick, Bartholome suggests that children
may be assisted in their moral education by participating in "nonthera-
peutic" research, once (at age five to seven) they are able to appreciate
the importance of helping others. As part of their general obligation to
enhance the moral development of such children, parents should encourage
them to take advantage of opportunities for moral growth; and Bartholome
contends that involvement in research is one of many activities which
parents might select to this end. He distinguishes between the parental
110
duty to encourage such behavior and McCormick's notion that parents
have a right to force children to engage in charitable acts. Bartholome
disagrees both with Ramsey's position that "children are not capable by
nature or grace of charitable acts" and with McCormick's position that
parents have a right to see that their children undertake such acts.
Instead, Bartholome considers the parental obligation to be one of moral
instruction, which may include encouragement but also requires that the
child be a willing participant. Assent by the child should be mandatory,
he maintains, and parents should be involved in the process both by
deciding whether or not participation in research would be a beneficial
learning experience for their child and by participating with their child
as "joint-subjects" when the experimental design provides an opportunity
for such collaboration. ■ - .
In an accompanying paper on "The Infant as Person," Bartholome takes
the position that infants (-c.e., children below the age of understanding)
have a right to be treated as persons but, because they have no awareness
even of themselves, do not have a moral obligation to the human community.
For this reason he would reject "nontherapeutic" research involving infants
below the age of five, at least where research requires serious invasive
procedures.
In the aforementioned pape*- by Hauerwas, Bartholome's position is cri-
ticized in two respects; first, because informed consent is taken as a pri-
mary issue and a necessary ingredient in respect for persons, and second,
because it is thought necessary that children be "persons" in order to have
111
rights and to merit protection, Hauerwas argues that third-person consent,
which Bartholome regards as an attempt to protect the child, might more
correctly be viewed as an attempt to protect the integrity of the family
unit by ensuring that whatever is done to a child is consistent with the
moral convictions and traditions of the child's family. Hauerwas argues
that children are deserving of care not because they are "persons," but
because they are children with a special position in a family unit. Their
rights, if they can be said to have rights, are claims against parents and
society for the provision of such care. For Worsfold and Bartholome to in-
sist that children be "persons" in order to participate in research, he
contends, is to make the mistake of requiring them to be adults in order
to be respected, which is to fail to treat them for what they are -- chil-
dren.
Hauerwas' argument, however, fails to appreciate either the merit or
the central problem in the moral instruction position promoted by Beecher
and Bartholome. The merit of the position on moral instruction proposed
by Bartholome is that it attempts a justification of research by appeal
to an actual contribution made to children. It is not implausible to sup-
pose that altruism can be cultivated in children by such "instruction,"
and these arguments are useful reminders that psychological and moral bene-
fits may be derived from participation in research (a type of benefit
apparently overlooked by Ramsey), On the other hand, these positions
(Bartholome' s, anyway) seem subject to the objection that whenever it could
not reasonably be said that a child would be instructed, the research could
not be justified. This position seems objectionable for some of the reasons
112
already mentioned in discussing Ramsey, since the argument partially re-
sembles Ramsey's highly restrictive position. Ramsey argues against al-
lowing research unless there is "therapeutic" benefit, whereas this posi-
tion stands against doing research unless there is moral benefit to the
child. As Bartholome correctly points out, even his own position would
exclude the entire class of "uninstructable" children. Unfortunately,
his contentions leave unanswered why it would be immoral or otherwise
wrong to involve uninstructable children such as infants. In short,
while this position may have merit by providing at least a partial justi-
fication for certain research, it fails to show that some research on
classes of children such as infants cannot be justified on a different
basis.
(5) A position with a conclusion similar to the presumed consent and
reasonable consent positions, but with a somewhat different theoretical
foundation, is that some research on children is justified because of the
beneficial consequences to the class of children in general. If this posi-
tion were stated in extreme form, it would be the unqualified utilitarian
position that such research ought to be done whenever it maximizes social
welfare to do so (whether or not the subjects assent or dissent). While
no writer seems to hold this unqualified position, two papers done for the
Commission give weight to the consideration of benefit to others as the
theoretical justification for research. The first paper was done by
H. Tristram Engelhardt, Jr.,-^^ and the second by Robert Veatch.-^' (Neither
paper, hovyever, deals solely or even primarily with research involving chil-
dren. )
113
Enjeihardt recognizes the absolutely fundamental character of both
the principle of respect for individual human subjects and the principle
of beneficence (which involves the concern to maximize benefits for society
in general), though he considers the protection of autonomy and promotion
of individual self-determination to be primary. Accordingly, he rejects
the involvement of unwilling subjects in research, even if the results
of the research v/ould be of considerable utility. ^ With respect to chil-
dren clearly too young to consent, he argues that "infants, though often
willful, have no free will and are not the object of respect as adults
are." Since infants are nonautonomous, there is no obligation to respect
autonomy; there is only an obligation to protect them from harm. He further
contends that the function of third-party consent in such contexts is not
to respect the child as an autonomous moral agent but to safeguard the
child's best interest by preserving his or her physiological and psycho-
logical integrity. But he regards the notion of third-party consent to be
less appropriate than other substitute language might be, since the third-
party feature contravenes the purpose of consent. The point of informed
consent, he argues, is to respect the freedom of individuals by asking
their permission before involving them in research, yet for many children
such treatment is impossible and inappropriate.
Engelhardt advances two sorts of arguments bearing on the use of chil-
dren in research. He first argues that research is nonallowable if it would
leave a residual amount of damage to the child. This argument stakes out
his restraining conditions on appeals to beneficial consequences. Although
his argument justifies research by appeal to beneficial consequences,
114
Engelhardt also advances one consequential ist argument v;hich actually
restricts research. He contends that investigators and parents should
always act in the best interest of children in order to provide general
support for social practices of attention and kindness to the defense-
less and powerless (a larger class than the class of children). None-
theless, Engelhardt concludes that experiments which may involve minor
discomforts but which would not expose children to physical or psycho-
logical risks greater than "in the usual ambience," are justifiable
"in terms of an appeal to the minimal duties that each of us owe{s)
to society. "■^■^ In this argument, his usually strong emphasis on indi-
vidual self-determination does not apply, and his argument turns on
the duties owed to society. These duties are grounded in beneficence
rather than respect for persons. -^^
Veatch agrees that "for the most part, it is a mistake to speak of
proxy consent for experiments in children", "^ however, parents may approve
a child's participation in "therapeutic" research because, as guardians,
they rightly serve to protect the best interests of the child, and as
parents they are given limited authority to exercise their own self-deter-
mination about their offspring, to the extent that their determination
does not substantially deviate from the social consensus. He argues
that parents may also encourage their children to make minor contributions
to the general welfare or to the welfare of specific others. He further
maintains that if "the individual is seen as a member of the social community,
then certain obligations to the common welfare may be presupposed even in
115
cases where consent is not obtained."-^'' This formulation expresses the
common thread of argument from beneficence running through the positions
of McCormick, Engelhardt and Veatch. This condition would apply, he says,
only in very special cases where there would be no risk or only minimal
risk to the subject and when the information to be obtained would be of
great social value and could be obtained in no other way. The subject's
participation in such research is justified, he contends, because of the
substantial contribution to the general welfare which may be made -- a
contribution which, even without consent, the "reasonable person would
find required. "-^8 (Veatch, however, adds that proceeding without consent
is valid only in the case of very young children where self-determination
is impossible. And he is always careful to add that his position does
not entail that social benefits can be used to justify a cancellation of
individual rights.) Veatch also argues in favor of retaining age 18 as
the age of consent for medical treatment, and favors adjudicating on a
case-by-case basis when, in the case of "therapeutic" research, children
and their parents disagree. Finally, he proposes that a national commit-
tee review all research protocols involving children, using the same re-
view criteria applied by IRBs.-^^
The qualified beneficial consequences position taken by Veatch and
Engelhardt would obviously be found deficient by Ramsey and Bartholome,
for example, on grounds that it justifies too much. In particular they
would argue that it fails to respect persons by subjecting them to risk
without consent and without obvious beneficial consequences for the sub-
jects. However, perhaps the largest potential deficit in the positions
116
taken by Veatch and Engelhardt rests in the lack of specificity concerning
the scope of research justified by their principles. For example, how much
research (if any) which involves more than minimal risk is acceptable in
"nontherapeutic" cases? It is hard to see how an answer could be derived
from their theory. Without further argument minimal risk seems a purely
arbitrary cut-off point when, in ^^ery special cases, substantial benefit
for others is in prospect. Both Veatch and Engelhardt are appropriately
engaged in the attempt to balance the obligation to protect individuals
against the obligation to provide substantial social benefits. While this
balancing must be done, it is doubtful that their theories satisfactorily
show how and at what point the individual rights of children properly limit
their social obligations. Relatedly, it is one thing to argue that some
research on infants may be allowed, and another to develop the precise
conditions under which it is justified. Neither Veatch nor Engelhardt
delineates a rigorous set of such conditions.
Among the well known dangers of social benefit approaches is that they
may justify so much on grounds of the principle of beneficence that the prin-
ciple of respect for persons fails to be applied.^ That is, the obligation
to benefit others (perhaps by developing therapies which avoid harm to them)
might be employed in such a way that the obligation to protect subjects is
not fulfilled. Both Veatch and Engelhardt attempt to guard against this
possibility, because, as Veatch puts it, there are such "great dangers" in
unqualified appeals to the benefit of others. Accordingly, what must be
said to be lacking in the Veatch and Engelhardt papers is not that they
117
make no appeal to the principle of respect for persons. What seems in
need of development is an explanation of the proper balance to be struck
between the competing obligations to respect persons and to benefit those
in need of help.
118
REFERENCES
1. Trials of War Criminals Before the Nuremberg Military Tribunals ,
U.S. V. Karl Brandt , vol. II, U.S. Government Printing Office,
1949, p. 181.
2. Leo Alexander, Psychiatry: Methods and Processes for Investigation
of Drugs, 169 Annals N.Y. Acad. Sci . , 1970, p. 347.
3. Andrew Ivy, The History of the Use of Human Subjects in Medical
Experiments, 108 Science 1948, p. 1. For an extended discussion
of this matter see Beecher, Research and the Individual: Human
Studies , Little, Brown & Co., Boston, 1970, p. 277.
4. Medical Research Council, Great Britain, Responsibility in Investi-
gations on Human Subjects (1963) in Beecher, op. cJjt. , pp. 262, 265.
5. Ibid.
6. World Medical Association, Declaration of Helsinki, 1964, in
Beecher, op. cit. , p. 277.
7. Ibid., p. 279.
8. DHEW, The Institutional Guide to DHEW Policy on Protection of Human
Subjects , DHEW Publication No. (NIH) 72-102, December 1, 1971. p. 7.
9. DHEW, Protection of Human Subjects, Policies and Procedures, 39
Federal Register 31742, November 16, 1973.
10. Ibid. , .' , '
11. Policy and Communications Bulletin , The Clinical Center, No. 75-5
(July 14, 1975). ^ ~ ,
12. 45 CFR § 46.103 (1975). ;
13. Paul Ramsey, The Patient as Person , Yale University Press, New Haven,
1970, p. 25.
14. Ibid., p. 39 (quoting Oscar M. Ruebhausen, Experiments with Human
Subjects, 23 Records of N.Y. Bar Association , Feb., 1968, p. 93).
15. Ibid., p. 12. .
16. Ramsey, Children as Research Subjects: A Reply, Hastings Center
Report , April 1977, pp. 40f,
119
See Chapter 3 of this report.
Ramsey does say, however, that benefits are sometimes unclear and
would make a difference in emergency situations. C^. The Patient
as Person , p, 15.
Ramsey, The Enforcement of Morals: Nontherapeutic Research on
Children, Hastings Center Report , August 1976, p. 21.
Benjamin Freedman, A Moral Theory of Informed Consent, Hastings
Center Report 5, August 1975, pp. 29-39. C^. esp. p. 38.
Richard McCormick, Experimentation on the Fetus: Policy Proposals,
Report Submitted to the National Commission for the Protection of
Human Subjects of Biomedical and Behavioral Research, 1975. In
Appendix: Research on the Fetus , DHEW Publication No. (OS) 76-128,
1976, pp. 5-3 and 5-4. For a fuller discussion by the same author,
see Proxy Consent in the Experimentation Situation, 18 Perspectives
in Biology and Medicine , Autumn, 1974, and Experimentation in Chil-
dren: Sharing in Sociality, Hastings Center Report , December 1976.
Children as Research Subjects: A Reply, p. 40.
The Enforcement of Korals: Nontherapeutic Research on Children, p. 24.
Stephen Toulmin, Fetal Experimentation: Moral Issues and Institutional
Controls, Report to the National Commission for the Protection of
Human Subjects of Biomedical and Behavioral Research, 1975. In Appen -
dix: Research on the Fetus , DHEW Publication No. (OS) 76-128, 1976,
pp. 10-7 and 10-8.
Victor Worsfold, A Philosophical Justification of Children's Rights,
Harvard Educational Review , vol. 44, no. 1, February 1974.
Ib-id. , p. 154, quoting Rawls, A Theory of Justice , Harvard University
Press, 1971, p. 249. -
Boston; Little, Brown & Co., 1970, p. 63. C|). W. J. Curran and
H. K. Beecher, Experimentation with Children, JAMA 10 (October 10,
1969), pp. 77ff.
The Ethics of Non-Therapeutic Clinical Research on Children.
120
30. Basic Ethical Principles in the Conduct of Biomedical and Be-
havioral Research Involving Human Subjects (December 1975).
31. Three Theories of Informed Consent: Philosophical Foundations
and Policy Implications (February 2, 1976).
32. Engelhardt, p. 7.
33. IbAxi. , pp. 36-37.
34. Tbld., pp. 35-37.
35. Veatch, p. 35.
36. Ibid. , p. 36.
37. Ibid., p. 37.
38. Jbld., p. 38.
39. Ibid., p. 49.
40. This form of reply to the Veatch and Engelhardt type of approach is
found in Hans Jonas' essay. Philosophical Reflections on Experi-
menting with Human Subjects, in Paul A. Freund, ed., Experimentation
with Human Subjects , George Braziller, Inc., New York, 1970. He
construes such research as a duty only in emergency situations.
121
Chapter 9. Deliberations and Conclusions
The Commission's recommendations on research involving children were
adopted unanimously with the exception of Recommendation (5), from which
Commissioners Cooke and Turtle dissented. Various members of the Commission
preferred different statements (or supported more than one statement) of the
rationale for their recommendations, and three such statements are included
below. Statements explaining the two dissents are also included.
Statement of Commissioners Height, King ,
Louisell, Ryan and Seldin
The Commission has identified three ethical principles that should under-
lie the conduct of biomedical and behavioral research involving human subjects;
beneficence, respect for persons and justice. In the case of research invol-
ving children, as in other difficult cases, the challenge is to find a proper
balance in applying these principles and to establish priorities among the
principles when they appear to be in conflict.
Beneficence . Beneficence requires both the provision of benefit and the
avoidance of harm. This principle is applied to research involving children
in several ways. The promotion of health, by improving methods to prevent
or treat a disease or abnormal condition and to foster optimal growth and
development, is a benefit that serves as a general justification of research.
Similarly, the imperative to avoid harm may serve as a justification for re-
search designed to evaluate the safety and efficacy of procedures in standard
123
practice. Avoidance of harm also requires that risk to human subjects be re-
duced or eliminated in the actual conduct of research.
In order to promote the health of both children and adults, the partici-
pation of children in research is needed. In many cases, children are the
only possible subjects for research designed to study the nature of childhood
disorders, some precursors of adult disorders, and the normal physiological,
psychological and social development of children. The benefits from such re-
search may accrue to the individual research subjects or to children as a
class.
Research also makes possible the avoidance of harm that may result from
the application of routine practices. This benefit is illustrated dramati-
cally in the case of infants, who cannot survive without the intervention of
others and for whom some previously accepted procedures have been proven
dangerous. Research has been required, for example, to learn the correct
levels of oxygen, fluids and nutriments that are necessary to sustain the
life of newborns without harming them. On grounds of beneficence, therefore,
the Commission considers the conduct of certain research involving children
to have strong ethical justification (Recommendation (1)).
The conclusion that research involving children may generally be justi-
fied on the grounds of beneficence does not mean that all such research is
therefore justifiable. The principle of beneficence also requires that those
who conduct or sponsor such research protect children from harm by limiting
the risk to which children may be exposed as research subjects. In Recom-
mendation (2) the Commission applies the principle of beneficence by delin-
124
eating general conditions that all research involving children should meet.
In Recommendations (3), (4), (5) and (6), the Commission addresses the problem
of determining the proper balance between the importance of conducting research
in order to promote health and the imperative to avoid harm to the children
who are subjects of that research. These considerations are reflected in pro-
visions regarding the nature of anticipated benefit that may justify the in-
volvement of children in research.
The Commission has concluded that problems related to two kinds of re-
search are comparatively straightforward. Where the risk of harm presented
to children by a research project is no more than minimal (Recommendation
(3)), no particular problems are presented so long as general provisions
are fulfilled (Recommendation (2)), and so long as appropriate provisions
are made for soliciting and receiving both parental permission and the
assent of the children who may be asked to participate (Recommendation (7)).
The second kind of research that presents relatively few ethical pro-
blems is that in which the risk is related to an intervention that holds
out a reasonable promise of benefit for the individual subjects. The ac-
ceptability of the risk presented by such an intervention should be determined
in the same way that the acceptability of risk is determined for interventions
that are applied in standard practice. Risk may be justified by an avoidance
of greater harm or by the provision of an important anticipated benefit to the
individual exposed to risk. Thus, if the anticipated benefit to the children
for whom the intervention is proposed is greater than the attendant risk, the
intervention is justified; and if the risk-to-benefit ratio of the proposed
125
intervention Is at least as good as that of other available approaches (in-
cluding refraining from any intervention), then the study of that interven-
tion is ethically acceptable even if the risks are more than minimal (Recom-
mendation (4)). The benefits that are expected to be derived from a thera-
peutic, diagnostic or preventive intervention, however, justify only the risk
associated with that intervention (including such procedures as may be neces-
sary, for reasons of safety, to monitor the effects of the intervention).
Risk associated with other procedures, performed purely for the purpose of
acquiring general izable knowledge, cannot be justified merely by inclusion
in a protocol that also includes procedures from which subjects may derive
direct benefit.
The most difficult ethical issues for the Commission arose with respect
to research presenting more than minimal risk but no immediate prospect of
direct benefit to the individual children involved. Some members of the
Commission urged that the limit for such research remain at the level of
minimal risk; others pointed out that such a limit might eliminate much re-
search that has great scientific significance and the promise of substantial
long-term benefit to children in general, while possibly avoiding only minor
additional risk to the research subjects. Much of the Commission's later
debate was focused on this class of research projects. The Commission was
seeking to determine the circumstances (if any) under which such research
might be ethically acceptable, and, if so, what review procedures would be
appropriate to assure proper protection of the research subjects.
In their resolution of this question, the Commission relied largely upon
two considerations. It noted, first, that the scope of parental authority
126
routinely covers a child's participation in many activities in which risk is
more than minimal, and yet benefit is questionable, (Involvement in skiing
and contact sports are two examples among many.) The Commission was also
impressed by reported examples of diagnostic, therapeutic and preventive
measures that might well have been derived from research involving risk that,
while minor, would be considered more than minimal.
Ultimately, the Commission decided (with two members dissenting) that
if three additional conditions are satisfied, research in this most difficult
class of cases could be justified (Recommendation (5)). First, the risk
involved must be only a minor increment beyond minimal. In addition, the
procedures to be used must be reasonably commensurate with (similar to)
those with which prospective subjects have had experience. Further, the
research must be likely to yield general izable knowledge important for the
understanding or amelioration of the subjects' specific disorder or condi-
tion. Thus, foreseeable benefit in the future to an identifiable class of
children may justify a minor increment of risk to research subjects.
In exceptional situations, dangers to children or the community re-
sulting from a failure to involve children in research might exceed what-
ever risk is presented by that research. For instance, the threat of an
epidemic that could be offset by developing a safe and effective vaccine
might justify research involving risk greater than otherwise acceptable to
establish safety, efficacy and dosage levels for children of different
ages. The outright prohibition of such research on grounds of risk might
constitute an exception to the general rules enunciated above, however, the
127
decision to permit its conduct should be made at the national level, with
opportunity for public participation. In Recommendation (6), the Commission
suggests procedures by which this goal may be accomplished. The same proce-
dures should be invoked to review any research that cannot be approved by
an IRB under the guidelines set forth in this document, whenever a review
board considers that for urgent or unique reasons the research should be
permitted.
Respect for persons . This principle requires that the choices of auto-
nomous individuals be respected. It is applied in the conduct of research
by asking permission of autonomous individuals before involving them as sub-
jects of research. Problems arise, however, regarding individuals with
diminished autonomy and thus diminished capacity to consent; and objections
to the involvement of children in research have been based on children's in-
capacity, or lesser capacity, to give valid consent to their participation
as subjects. Indeed, most of the literature has focused on this problem,
and the most restrictive position (exemplified by Ramsey) is that children
should not be involved in any research unless it is reasonably expectable
that they will derive some direct benefit from their participation.
The Commission considered seriously the arguments presented by those
engaged in the current debate about the legitimacy of third-party consent
(see Chapter 8 of this report). The Commission concluded that the incapacity
of children to consent is one aspect of a more general condition of depen-
dency on adults who are responsible for their care. The permission that
parents give for children's participation in research can be accepted as
128
an exercise of their general role, as caretakers, to guide decisions af-
fecting their children's lives and activities. Although some critics have
challenged the right of parents to make decisions for their children to
participate in research, the Commission is persuaded that the practical need
for parents to manage the details of the child's life legitimately extends
to such decisions, •.• . ,^.. •. . . . -
One consideration that does justify the placing of limits on parental
or guardian authority is respect for the developing autonomy of children.
The Commission has concluded that any child capable of some degree of under-
standing (generally, a child of seven or older) should participate in re-
search only if the child assents. Even the objection of a very young child
should be binding except for situations in which the research involves a
therapeutic intervention that is unavailable outside the research context.
This conclusion is consistent with a recent trend in both law and philoso-
phy to respect the rights of children and to encourage their development
toward assuming responsibility for their decisions. It is also consistent
with the reported ability of children of school age to make decisions con-
cerning their activities (see Chapter 6), and with the practice of investi-
gators in pediatric research who commonly seek the assent of children at
seven years of age and older before accepting them as research subjects
(see Chapter 3).
Recognition of the capacity and the right of children to make their
own determination regarding participation in research resolves important
ethical problems about third-party consent. By respecting the developing
129
autonomy and moral responsibility of children (as proposed by Worsfold and
Bartholome and to some extent by Engel hardt and Veatch), the problem of
involving children in resea; ch against (or without) their will is avoided.
This conclusion does not resolve the considerable difficulties that may
arise in determining how informed and responsible some children are, and
thus is not to be construed as an unrealistic application of the principle
of respect for persons. One unresolved area concerns the involvement of
infants and children who are incapable of assenting or of objecting to
their participation. For this class of children, the Commission believes
(as anticipated by Veatch and Engelhardt) that benefits either to the sub-
jects or to the class of children may justify the involvement of children
who are unable to indicate willingness or unable to object, provided their
parents (or some other appropriate third party) protect their physical and
psychological integrity throughout the research project, and provided further
that strict limitations are placed on the risk to be permitted.
It must be recognized that there may be occasions when parental or
guardian interests are at odds with the best interests of their children.
When parental permission cannot be relied upon as a protective mechanism
(as in cases of child abuse, for example), alternative mechanisms should be
set in place to protect the health and welfare of the children. In other
instances (for example, when the research involves treatment of conditions
such as venereal disease or drug abuse) a requirement for parental permis-
sion may actually jeopardize the health or welfare of a child. In the lat-
ter cases, the assent of the child should be sufficient as it now is in those
130
jurisdictions where children may consent on their own to treatment of such
conditions. (The Commission's conclusions regarding consent are reflected
in Recommendations (7) and (8).)
There are several additional conditions that respect for persons re-
quires in the conduct of research: e.g., that the time and inconvenience
requested of subjects be justified by the importance of the research and by
the soundness of its design, even if no more than minimal risk is involved;
that the privacy of children and their families be protected; and that the
confidentiality of data be maintained. (These conditions are set forth in
Recommendation (2).)
Justice . Justice is a moral principle that requires a fair distribu-
tion of burdens and benefits in a given population. In research contexts
this principle requires that the burdens of being involved in research
should be fairly distributed and that the benefits produced by the research
also should be fairly allocated. There are at least two dangers of injustice
that might result from the involvement of children in research. First, cer-
tain groups of children may be overutilized as research subjects due to their
ready availability. For example, there are manifest dangers that children
living in orphanages or in special training facilities might be exploited for
purposes of research. Given their dependent status and their diminished capa-
city to consent, it is important that children be protected against selection
solely because of administrative convenience or because their illness or socio-
economic condition render them especially vulnerable. It does not follow that
such groups of children can never be involved in research. The point is that
since there is a relevant inequality in their situation, they should not be
131
treated in the same way all other children are treated; rather, they should
be afforded additional protection. However, it may be justified to involve
that class of children in research concerning their specific condition. This
conclusion is an application of the formal principle of justice that equals
should be treated equally, while those unequal in morally relevant respects
may be treated unequally.
Second, wherever appropriate, animal and adult studies should be con-
ducted prior to the involvement of children in a research project. Studies
on older children should also be conducted prior to the involvement of younger
children and infants. This distributive principle is itself justified by
certain conclusions already derived from the principles of respect for per-
sons and beneficence. Respect for persons requires obtaining informed con-
sent whenever possible. Since informed consent is far more likely to be
obtained in a meaningful way from the adult population, and since older
children can be more easily informed than younger ones, respect for persons
dictates that adults and older children be respectively first and second in
the order of persons selected as subjects of research. Beneficence also
plays a role because it is easier to avoid doing harm to adults and older
children than to younger ones. Young children often do not accurately re-
port their feelings or physiological responses, and investigators are thus
not likely to know if something unusual occurs. Accordingly, infants might
be at greater risk than adults participating in the same research. In short,
beneficence and respect for persons provide a dual justification for the
claim that, as a matter of distributive justice, research risks should be
allocated to adults rather than to children whenever feasible. Justice also
132
requires that special classes of children not be inequitably selected as
research subjects -- no matter how significant the research may be (Recom-
mendations (2), (9) and (10)).
Statement of Commissioners Brady. Jonsen, Lebacqz ,
Louisell, Ryan and Stellar
During the course of its deliberations, the Commission has recognized
that biomedical and behavioral research brings about certain benefits for
individuals and society. Discovery of new information, improved understand-
ing of the human condition and the environment, better treatment of disease
or other disorders: these are the obvious benefits to individual subjects
and to society that have resulted and continue to result from research.
Insofar as research is directed to these goods, it manifests the ethical
principle of conferring benefit and avoiding harm. This is the first of
the ethical principles that the Commission has identified as underlying
the conduct of research.
In the case of research with children, it is obvious that significant
benefits for individual subjects and for society have been produced. Parti-
cipation of children in research has led to many discoveries that have im-
proved the health of children. Children are often the only possible subjects
in those investigations studying the normal physiological, psychological and
social development of children, the nature of diseases peculiar to children,
and the childhood precursors of disorders that are manifest only during adult
years. In addition, research uncovers, and makes it possible to prevent, harrr
that results from some common and routine practices of dealing with children.
133
This benefit is dramatically illustrated in the care of infants, who cannot
survive without the intervention of others and for whom some standard medical
procedures have been proved dangerous. Research has been required, for exam-
ple, to learn the correct levels of oxygen, fluids and nutriments that are
necessary to sustain the life of newborns without harming them. In the light
of such evidence, it is obvious that biomedical and behavioral research in-
volving children conforms to one essential ethical principle: it contributes
to the good of individuals and, consequently, to society while also contri-
buting to the avoidance of harm. . ^
However, it is also obvious that research involving children encounters
major ethical objections, for, while much of such research involves nothing
more than observing and recording the activities of children, some investiga-
tions seek information that can be obtained only by exposing the subjects to
some risks that would not otherwise be part of their lives or their care.
That same principle of conferring benefits also requires, not only that harm-
ful current practices be revealed, but that harm to individuals be avoided.
Thus, research with children, to the extent that it involves any exposure
to otherwise nonexistent risks, raises a serious ethical question and calls
for particular ethical justification. In addition, some assert that even
where harm is not an issue, the researcher breaks into the privacy of the
child in a way that is not ethically justified. For example, one author
asserts that "children can be vfl"onged, without being harmed."
In the case of research with adults, the problem of risk and the problem
of privacy, as a rule, can be answered by insisting on the free consent and
134
informed consent of the participant in research. The practice of generally
requiring free and informed consent of adult subjects, which is recognized
by all recent codes of ethics of research, rests upon the second major prin- '
ciple that the Commission has identified as underlying the ethical conduct
of research: the principle of respect for persons. This principle can be
understood as the source of the obligation that all persons be allowed to
select and follow those courses of action which they judge good for themselves,
unless their activities cause harm to others. In accordance with this princi-
ple, research participation ought never to be imposed on individuals against
or without their willingness, provided they are capable of expressing their
willingness. However, the principle of respect for persons can be stated in
a more fundamental manner. It established the obligation that each person be
acknowledged as a unique being, and dealt with in terms of his or her own
desires, needs and purposes. If the person is capable of communicating those
unique desires, needs and purposes, that expression becomes the first and, in
most cases, the final and deciding factor in how others ought to act toward
them. Children are often absolutely incapable of such communication; when
they can communicate, they may do so only imperfectly. Children's desires,
needs and purposes are imperfectly developed, their self -understanding and
understanding of the world is incipient, and their judgments, when formulated,
are limited. Still, the ethical principle of respect extends to them: it de-
mands respect for their reality as children. This respect requires protection
of their evolving autonomy, a protection which should lead them toward maturity
and, at the same time, shelter them from harm which they cannot themselves ward
off.
135
Finally, whatever benefits issue from the research should be distributed
throughout the society in ways that are fair, and the burdens of any research
that is permitted should not fall unduly on certain persons or groups. Thus,
the principle of justice, identified by the Commission as the third ethical
principle, supplements the principles of respect and conferral of benefits.
The Commission considers that all of these principles must be taken to-
gether as the necessary and sufficient conditions for the ethical conduct of
research regarding children. Unless research can be designed which reflects
all three, it cannot be called ethical. However, the Commission admits that
the production of benefit, the avoidance of harm, respect for persons, and
justice are complex notions that must be refined in ways which, on the one
hand, make them more specific and, on the other, remain true to their essen-
tial meaning. Its deliberations were directed toward an attempt to view re-
search with children within the perspective of all these ethical considera-
tions. Its conclusions reflect the difficult effort to interpret these prin-
ciples and to make appropriate distinctions in their application to the various
general situations found in research involving children.
Recommendation (1) states the Commission's conclusion that the evidence
bears out the social value of research with children. It also states that the
Commission is satisfied that the benefits of research can be sought in ways
that meet the ethical standards that ought to underlie the conduct of all re-
search. Recommendation (2) proposes that reasonable and informed persons, in
judging whether any proposal for research with children meets ethical standards,
should invariably demand assurance on several points. Considerations of pro-
136
viding benefit and avoiding harm are reflected in the provisions that re-
search be scientifically sound and significant and that its risks be mini-
mized. Considerations of respect are reflected in the provisions about
protection of privacy and confidentiality. Considerations of justice are
reflected in the provisions to conduct studies first on animals or adults
and to select subjects equitably. -
Recommendation (3) applies the principle that harm should be avoided.
It acknowledges that where no risk at all or no risk that departs from the
risk normal to childhood (which the Commission calls "minimal risk") is
evidenced, the research can ethically be offered and can ethically be ac-
cepted by parents and, at the appropriate age, by the children themselves.
The Commission has taken this position because it has concluded that the
scope of parental responsibility includes the right to choose activities and
to define a manner of life for their children. It is inevitable that many
activities and events of childhood involve some risks. No one suggests that
parents must shield their children from all risks; some propose that permit-
ting only those risks of activities likely to benefit the child lies within
the parental prerogative. The Commission considers this position too strin-
gent and artificial, since many of the experiences which parents generally
allow to their children are somewhat risky and cannot be said, without forcing
the case, to involve particular benefits. The Commission, then, has concluded
that, when risks entailed in research are equivalent to normal risks of child-
hood, parents may properly permit these risks.
Recommendation (4) applies the principle of conferral of benefits to the
situation in which a particular child 1s the intended beneficiary of an in-
137
tervention which does entail risks "more than minimal." Whenever benefits
and harm may accrue to the same person and when that person has some needs
that require remedy, it has long been considered ethically appropriate to
"balance" the risks and benefits and to proceed on the showing that "bene-
fits outweigh the risks." The Commission has taken this concept a step
further. It has decided that the justification of the contemplated course
of action on the basis of the risks and anticipated benefits associated with
it should be at least as strong as the justification on the basis of risks '
and anticipated benefits of any other course of action (or nonaction). Un-
questionably, this sort of calculation is a matter of discretion. It cannot
easily be expressed in quantitative terms, although in some cases statisti-
cal data about possible benefits and risks can be adduced as evidence. In
the last analysis, the concerned parties, namely, the researchers, the re-
viewers, the parents and, if possible, the child, must attempt to form a judg-
ment of acceptability.
Recommendations (5) and (6) represent the most difficult problem in
reconciling all appropriate ethical principles. This problem arises when
interventions dictated solely for research purposes, with no intention of
benefiting the subject, present more than minimal risk. Some members of the
Commission urged that the limit for risks of any interventions not intended
to benefit the subject be held to the conservative level of "minimal risk";
others pointed out that such a limit would proscribe much research that pro-
mises substantial future benefits to many children. Much of the Commission's
later debate centered on this class of research projects.
138
Most of the Commissioners agreed that a minor increase in risk would
be permissible in order to attain substantial future benefits to children
other than the subject. "Minor increase" refers to a risk which, while it
goes beyond the narrow boundaries of minimal risk determined by the Commis- ■■
sion, poses no significant threat to the child's health or well-being. More-
over, the Commission requires that the research activities presenting such
risks be similar to the experiences familiar to the children who would be
the subjects of the research. Such activities, then, would be considered
normal for these children. Given this conservative limit, the Commission
concluded that promise of substantial benefit does justify research which
goes beyond, but only slightly beyond, the minimal risk. The Commission con-
siders that, as in the question of "no more than minimal risk," permission
to allow such research lies within the scope of parental responsibility. In
addition, children capable of more mature judgment may wish to volunteer for
research of this sort. . ,'
Ultimately, the Commission decided (with two members dissenting) that
if three conditions are satisfied, research in this most difficult class of
cases could be justified (Recommendation (5)). First, the risk involved
must be only a minor increment beyond minimal. In addition, the procedures
to be used must be reasonably commensurate with (similar to) those with
which prospective subjects have had experience. Finally, the research must
be likely to yield knowledge important for the understanding or amelioration
of the subject's specific disorder or condition from which the subject suf-
fers, even though the subject may not actually benefit. Thus, foreseeable
139
benefit to an identifiable class of children may justify a minor increment
of risk to research subjects.
The Commission acknowledged that exceptional situations may arise in
which considerable dangers to children or to the community at large might
be avoided or prevented by exposing children to research attended by more
than minimal risk. Some might offer the ethical argument that avoidance
of great danger or disaster outweighs the injunction against exposing chil-
dren to risk of more than minimal harm. For instance, they may say the
threat of an epidemic that could be offset by developing a safe and effec-
tive vaccine might justify research involving risk greater than otherwise
acceptable to establish safety, efficacy and dosage levels for children of
different ages. The outright prohibition of such research on grounds of
risk might have consequences which themselves appear unethical.
Faced with such a hypothetical situation, the Commission found itself
confronted by a common dilemma: regardless of whatever course is chosen,
some benefit may be foregone and some harm may be done. Rather than attempt
to resolve the dilemma in the abstract, the Commission has chosen to recom-
mend that the ethical argument should be made, not over a hypothetical case,
but over an actual situation, in which the real issues and the likely costs
of any solution can be more clearly discerned. The ethical principles at
stake are the moral obligation to protect the community or to come to the
aid of certain sufferers within it and the moral prohibition against using
unconsenting persons, at considerable risk to their v^ell-being, for the pro-
motion of the common good. These principles are of such moment end their
140
observance so basic to a just and humane society that any debate about their
application should be held at the most public level of discourse. Thus,
Recommendation (6) urges that should such a situation occur, it be defined
in the most stringent way and determined by those at high levels of public
accountability. • ■
The central point of contention in the debate over the ethics of research
involving children is the question of consent. The codes of ethics of experi-
mentation and almost all commentators agree that free and informed consent of
the subject should be required for participation; however, as we have noted
in Chapter 8, they are ambiguous regarding children. When they do admit the
participation of children, they do so on condition that proxy consent is granted
by parents or guardians. Proxy consent, of course, is not free and informed con-
sent of the subject, but rather the permission of another.
Recommendations (7) and (8) deal with issues related to "informed con-
sent." As noted above, the requirement to seek informed consent derives from
the principle of respect for persons. This principle means both that the free
choices of persons should be respected and that their individual needs, desires
and life situations be acknowledged and honored. The Commission admits that
infants are quite incapable of consent and that children exhibit in varying
degrees the activities which can be recognized as understanding and consent.
Since children are not autonomous, that is, fully capable of informed, re-
flective decisions, other aspects of their life situation besides autonomy
are important in determining what "respect for persons" requires. The Commis-
sion decided that the dependence of children on adults, which is both the
141
condition for their growth and the source of their vulnerability, is ethi-
cally relevant. Moreover, the Commission acknowledges and affirms the im-
portance of the family in the child's life: to be a child is, generally,
to be a member of a family. Respect, then, requires that children be pro-
tected from influence and circumstance that would (in the case of children,
at least) impede their growth or compromise their health, safety or future
well-being. In the case of children, this calls for an awareness of the
limits and the potentiality of childhood, at varying steps in its develop-
ment, as well as acknowledgement of the social milieu in which children live.
The Commission reached the conclusion that, as a rule, decisions about
the participation of children in research should reflect a combination of
respect for the general prerogatives of parents in protecting the health
and safety of their children and respect for the maturing autonomy of the
child. The Commission, therefore, recommends that the IRB assure adequate
provisions are made for soliciting assent and permission (Recotmiendation (7)),
It also suggests that the objection of a child to an intervention imposed
for research purposes alone should generally be binding. In so doing, it
permits the child to protect itself from unpleasant experiences and respects
the maturing autonomy of the child. In view of the presumption that very
small children are specially vulnerable and that parents are generally the
best protectors of their children, the Commission also recommends that the
IRB consider whether parents should be intimately involved, sometimes even
present, in research activities that may disturb very young children or in-
fants. ,
142
The Coiranission also notes that childhood is a changing state and that
children become progressively more capable of reflective choices. Empirical
studies have revealed the maturationj at particular ages, of children's
ability to make ethical judgments. While there is debate about precise ages,
the Commission has selected age seven as the age that may be considered as
the time when children become capable of some reflective judgment. For pro-
cedural purposes, it imposes this age as the suitable time to consult the
child about research. Since some research bears no benefit to such child,
the Commission has decided that, in such cases, the child's refusal to parti-
cipate should be determinative. In those cases where investigational proce-
dures are being done with specific therapeutic intent and hold out the prospect
of benefit that is available to the child only in the context of research, the
Commission, recognizing the imperfect nature of a child's assessment of cir-
cumstances, allows the parental judgment to be final.
The Cojimission notes that the growing autonomy and privacy of children
is recognized by some jurisdictions, where older children are permitted to
give consent for specific medical interventions. Moreover, Commissioners
were aware that informing some parents of proposed research involving their
children might jeopardize rather than contribute to the child's welfare
(e.g.. In cases of venereal disease or child abuse). Thus, the Commission
recommends that whenever parental permission Is not a reasonable requirement
to protect the well-being of the child, alternatives should be required by
the IRB (RecoiTsuendatlon (8)). Here, it operates under the general moral
principle to avoid harm as well as to respect the autonomy of older children.
In addition, the Commission recognizes that some parents are unsuited to
143
care well for their children, and that some children are without caring
parents. In these situations, the Commission requires an advocate for the
child, to take the place of a parent (Recommendation (9)). i
Finally, Recommendation (10) requires that additional special protec-
tions be invoked where children are institutionalized.
Statement of Commissioner Louisell
I hope that the alternative ethical rationalizations of the Commission's
recommendations will not produce confusion. Each I think is an acceptable
position paper so far as it goes. The assumed need for both reflects, I be-
lieve, the grave and inherent difficulty occasioned by Recommendation (5),
which deals with potentially nontherapeutic experimentation involving more
than minimal risks. Such experimentation on children can be morally justi-
fied, if ever, only to fulfill an essential social need analogous to that
involved in the drafting of youth for national security purposes. Resolu-
tion of this kind of a moral dilemma in a democracy at a minimum requires
decision by society's highest political voice, and that is why I have in-
sisted upon Congressional review as a condition of this type of experimenta-
tion.
Caution respecting experimentation on children can hardly be excessive,
especially in an era when new inhibitions on the power of government to pro-
tect children are surprisingly found in the Constitution itself. Carey v .
Population Services Internationa l, 97 Sup. Ct. 2010 (1977).
144
Dissenting Statement of Commissioner Cooke
Recommendation (5) permits the involvement of infants and children who
are unable to consent in research which is highly important to reduce harm
to other individuals with similar conditions at some subsequent time, but
which offers no prospect of immediate or delayed benefit to the subjects
despite the confusing implication of section (C) that the subjects' disor-
der might be ameliorated. If the subjects were truly able to volunteer
rather than parents volunteering them, such a recoimendation would be ac-
ceptable even though the risk exceeds minimal. Further, if the risk were
no more than what is commonly understood to be " minimal " -- that is, only
a slight additional risk beyond that of everyday life -- parental permis-
sion would be acceptable if the parents (one or both) also participated in
the research and could withdraw the infant or child if discomfort seemed
excessive.
By the designation of acceptable risk as that beyond minimal even to
a "minor" degree, the Commission transfers to each Institutional Review
Board the decision regarding the limits of "minor." Although a process is
provided for judging "minor," no traditional guidelines exist nor are any
examples provided. Considerable disparity can then be expected in such de-
terminations by one IRB or another.
This recommendation does avoid the cumbersome transfer of much research
approval to a National Ethical Advisory Board, but because of the differences
in IRB performance it is likely that ethical review will be carried out by
the NIH study sections, which will be forced to operate as a surrogate National
145
Ethical Advisory Board, but without public debate or exposure as required
in Recommendation (6).
In the ethical justification of its recommendation the Commission can
invoke only the principle of utility. This in itself does not constitute
any breach of ethics, but it does indicate the perilous nature of the recom-
mendation and the ethical uncertainty of the Commission.
Dissenting Statement of Commissioner Turtle
Preliminary Statement -
Throughout the Commission's deliberations, I have expressed many reser-
vations about the involvement of children as research subjects. My fellov/
Commissioners have heard me out in each instance and accommodations have
been reached in all areas* except one -- the special status, if any, to be
accorded sick children with regard to their potential involvement as research
subjects where no foreseeable benefit will accrue to the subject.
I believe that the substantial majority of the Commission (9-2) has com-
mitted clear error in approving Recommendation (5), potentially subjecting
* My problems with "proxy consent" have been dealt with by obtaining parental
permission and children's assent and in recognizing that a child's objec-
tion at any stage of the project is determinative. This protection is simi-
larly afforded to infants through encouragement of the participation of a
parent in those situations in which the child is clearly dependent (Recom-
mendation (7)). The problem of an Executive "kiddie draft" for more than
minimal risk research in response to another "swine flu" scare is ameliorated
by the requirement for Congressional notification and real opportunity for
debate and action (Recommendation (6), Comments).
sick child, :n to greater risks than other children without regard to fore-
seeable benefit, and thus, I must register this dissent to that Commission
recommendation.
Conclusions
1. Sick children cannot be deemed to be a morally relevant separate
class for purposes of relaxing protective measures and mechanisms.
2. Sick children, if capable of being placed into a morally relevant
separate class, would require even greater protection than that afforded to
children in general .
3. The distinctions attempted in both sets of deliberations* are shams
and there is no legal, ethical or social basis for subjecting sick children
to more than minimal risks merely because a foreseeable benefit might accrue
to an identifiable class of children in the future.
Argument
1 . Sick Children Cannot be Deemed to be a Morally Relevant Separate
Class for Purposes of Relaxing Protective Measures .
Only one set of deliberations presents any argument for affording less
protection to sick children than to all other children. It posits that sick
children are by the very nature of their condition subject to certain unique
* The Commissioners have presented two sets of deliberations, the rationale
for the majority position on Recommendation (5) is found at pages 125 througi-
127 and 138 through 140 of this report.
147
risks and experiences, and relies on the limitation that added research
"risks be similar to the risks and experiences familiar to certain classes
of children" to conclude that the added research risks "are normal for
these children." This rationale is a perversion of the Commission's at-
tempt to define "minimal risks" as relating to the ordinary everyday risks
of childhood.
Children, who through no fault or choice of their own, are subjected
to greater risks incident to their condition or necessary treatment, cannot
ethically be assumed to qualify for additional increments of risk. To do
so, is to add to the potential burdens that result, directly or indirectly,
from the child's illness. This is especially true when the Commission places
more restrictive liniits on the involvement of normal children (Recommendation
(3)). The natural and intended consequences of providing restrictive limits
on one subject group, and relaxing limits on another, is a direction to re-
searchers to involve more sick children as research subjects. Nowhere is
such a direction countered by any requirement that research projects not
involve sick children if normal children would likewise be scientifically
appropriate subjects. ■
Taken as a whole the Commission's recommendations mandate that research
involving more than minimal risk will be carried out on sick children, sim-
ply because they already are subject to similar or greater risks. The aggre-
gate impact of risks is ignored and the burdens of research "fall unduly" on
the sick child in clear violation of the Commission's own formulation of the
principle of "justice." " '
148
The aggregation of risks concept and the impact of sickness on other
protective mechanisms would, if properly assessed, require that sick chil-
dren be segregated from others for purposes of special protection as des-
cribed below.
2. Sick Children, if Capable of Being Placed into a Morally Relevant
Separate Class, Would Require Even Greater Protection Than Others .
a. The Principle of Beneficence Must be Applied . The Commission has
adopted as one of its basic ethical principles the principle of beneficence.
This principle which directs, at the least, that we do no harm requires
that those who, by virtue of their condition already experience greater
than normal risks, should be protected against any increment of risks, no
matter how slight. Thus, in assessing risks to a subject in both a legal
and ethical sense, it is necessary to take into account the known fragility
of the subject as a result of his existing conditions before creating a
situation in which any increment of risk, no matter how minimal, can be
added. There are some societies which do not grant equal value to the
sick and the healthy. It has always been my assumption that our society
was not among them and that we considered that we had a special need to
protect and assist those, who through no fault of their own, might be at
a disadvantage or most vulnerable. The Commission's Recommendation (5) is
directly contrary to my understanding of the principle of beneficence as it
is applied in our society.
b. Other Protective Mechanisms Which Generally Supplement the IRB
May be Adversely Affected in the Case of a Sick Child . The Commission has
149
recognized that IRB review is not the only protective mechanism which is
available to children. Specifically, we have required parental permis-
sion, children's consent and have given the child a veto with regard to
involvement in a research project.
The Commission did not specifically assess how well these other pro-
tective mechanisms would v/ork with sick, as opposed to normal children.
However, evidence in the record tends to support the general proposition
that such protective mechanisms are not enhanced, but rather are diminished,
when the prospective subject is a sick child.
First with regard to the child, the illness itself may be such as to
interfere with normal cognitive and physical functions involved in the abi-
lity to assent meaningfully and even more important the ability to object
at any stage of the project. This is especially true of children who are
suffering from some form of mental retardation or are under the influence
of some drug or sedative necessary to their therapy at the time that their
participation is both solicited and effected.
Second, children who suffer long bouts with illness develop a special
relationship with their therapist and the medical staff. To a certain ex-
tent because of their separation from their normal parents, the therapists
and staff themselves often become surrogates for parental authority. When
those therapists and medical staff are involved in a research project, the
child's assent or failure to object may be influenced by the surrogate
parent relationship.
150
With regard to parents there are certain obvious impacts on both the
family unit and the parent that result from a child's illness. First, the
emotional impact of a serious illness in the family may lead to a breakdown
of the judgmental and perceptive relationships within the normal family unit.
To a certain extent, the sick child becomes a burden that parents may not
be capable of assuming without some diminishing of normal parental judgment
and discretion. This is especially true in situations in which the child
must be confined to an institution in order to obtain therapy or treatment.
It is also true of those situations in which therapy or treatment at home
is especially difficult and disruptive. Second, the parent of the sick
child will in most instances have a long, intimate, and even emotional in-
volvement with those who provide therapy for the child. As amply demonstrated
in some of the filmed informed consent sequences presented to the Commission,
that emotional involvement with the therapist may well have a severe and in
fact even overriding impact on the parents' judgment with regard to granting
permission for the participation of their child in a research project.
In conclusion then both the principle of beneficence, and the adverse
impact on the other protective mechanisms require that this Commission afford
sick children greater protection than that afforded to children at large.
3. The Distinctions Attempted in Both Sets of Deliberations are Shams and
There is No Legal, Ethical or Social Basis for Subjecting Sick Children to
More Than Minimal Risk Merely Because a Foreseeable Benefit Might Accrue to
an Identifiable Class of Children in the Future.
151
In its two sets of deliberations, the Commission has attempted to pre-
sent a shopping list of reasons in support of Recommendation (5). Each of
these shall be dealt with separately, below.
First, the Commission notes that "the scope of parental authority
routinely covers a child's participation in many activities in which risk
is more than minimal, and yet benefit is questionable (involvement in skiing
and contact sports are two examples among many)." Without concurring in the
judgment of the Commission that benefit in skiing and contact sports is ques-
tionable, it is clear to me that this same rationale holds true for normal
children as well as sick children. Thus, I perceive no basis for making
any distinction between the two classes of children on the basis of that state-
ment.
Second, the Commission notes that it was "impressed by reported examples
of diagnostic, therapeutic and preventive measures that might well have been
derived from research involving risks that, while minor, would be considered
more than minimal." Again, that rationale provides no basis for segregating
children into separate classes. The rationale is strictly utilitarian and,
is not specifically supported in the record. Moreover, at no point does the
Commission require that such research be carried out only if normal children
would not be scientifically appropriate subjects. In the absence of such a
limitation, I do not believe a strictly utilitarian rationale can provide
adequate justification for a policy creating a doubly disadvantaged class of
children.
152
Third, the Commission suggests that more than minimal risk is a con-
dition that is "normal" for sick children. My problems with that charac-
terization have been expressed above and will not be repeated here.
Finally, both sets of Commission deliberations conclude that "foreseeable
benefits in the future to an identifiable class of children may justify a
minor increment of risk to research subjects." That statement can be used
to justify large quantities of applied research utilizing sick as opposed to
normal children. The statement itself is without legal, ethical or social
justification. If such justification did exist, it could be applied equally
as well to normal children. In a situation in which "conservative" limits
are placed on the participation of normal children, relaxation of those limits
for sick children constitutes a specific mandate and direction to shift the
risks and burdens of research from children in general to those who, by nature
of their illness, are least, and not most, appropriate research subjects.
Comment by Dr. Ryan, Chairman of the Commission
In spite of the diversity of views reflected in the foregoing statements,
our recommendations were adopted almost unanimously. The dissenting statement
of Commissioner Turtle reflects a sharp disagreement, however, and requires
some comment since it is based, I believe, on a misunderstanding of Recommenda-
tion (5).
The Commission has adopted a conservative definition of "minimal risk,"
X.e. , the risk of harm that is normally encountered in the daily lives, or in
153
the routine medical or psychological examination, of healthy children. Vir-
tually the entire Commission is in agreement that a "minor" or "slight" addi-
tional risk over that normally encountered may ethically be presented in very
limited circumstances by research not intended to benefit directly the chil-
dren who are subjects. These limited circumstances are commensurability of
experience, likelihood of yielding general izable knowledge about the subjects'
disorder, and importance of that knowledge for understanding or treating such
disorder. Further, provision must be made, when appropriate, for the parti-
cipation of parents in such research .involving their children.
Recommendation (5) contemplates research into the nature and treatment
of disorders that specifically afflict children. The limited circumstances
under which such research may be approved under Recommendation (5) clearly
indicate that the research must be related to the disorder or condition af-
fecting those subjects who are involved. Such research cannot by its very
nature be conducted on normal subjects. Accordingly, Mr. Turtle's statement
that the Commission's recommendations require research presenting more than
minimal risk to be carried out on sick children merely because they are al-
ready subject to such risk, and his contention that the recommendation would
shift involvement in such research from normal to sick children, are both in-
correct. The Commission's intention in Recommendation (5), and the likely
effect of this recommendation, are clearly not to encourage any unnecessary
involvement of sick children in research, but rather to permit the conduct of
research intended to develop important knowledge of disease states from which
certain children suffer and for which research they are the only appropriate
subjects.
15^1 " <KJ.S. GOVERNMENT PRINTING OFFICE; 1977 241-161/3114 1-3
NIH LIBRARY
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U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
DHEW PUBLICATION NO. (OS) 77O004
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